---
_id: '14683'
abstract:
- lang: eng
text: "Mosaic analysis with double markers (MADM) technology enables the generation
of genetic mosaic tissue in mice and high-resolution phenotyping at the individual
cell level. Here, we present a protocol for isolating MADM-labeled cells with
high yield for downstream molecular analyses using fluorescence-activated cell
sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion,
single-cell suspension, and debris removal. We then detail procedures for cell
sorting by FACS and downstream analysis. This protocol is suitable for embryonic
to adult mice.\r\nFor complete details on the use and execution of this protocol,
please refer to Contreras et al. (2021).1"
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: This research was supported by the Scientific Service Units (SSU)
at IST Austria through resources provided by the Imaging & Optics Facility (IOF)
and Preclinical Facilities (PCF). N.A. received support from FWF Firnberg-Programme
(T 1031). G.C. received support from the European Union’s Horizon 2020 research
and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411
as an ISTplus postdoctoral fellow. This work was also supported by IST Austria institutional
funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European
Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780
LinPro) to S.H.
article_number: '102771'
article_processing_charge: No
article_type: review
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Giselle T
full_name: Cheung, Giselle T
id: 471195F6-F248-11E8-B48F-1D18A9856A87
last_name: Cheung
orcid: 0000-0001-8457-2572
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Amberg N, Cheung GT, Hippenmeyer S. Protocol for sorting cells from mouse brains
labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols.
2023;5(1). doi:10.1016/j.xpro.2023.102771
apa: Amberg, N., Cheung, G. T., & Hippenmeyer, S. (2023). Protocol for sorting
cells from mouse brains labeled with mosaic analysis with double markers by flow
cytometry. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2023.102771
chicago: Amberg, Nicole, Giselle T Cheung, and Simon Hippenmeyer. “Protocol for
Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers
by Flow Cytometry.” STAR Protocols. Elsevier, 2023. https://doi.org/10.1016/j.xpro.2023.102771.
ieee: N. Amberg, G. T. Cheung, and S. Hippenmeyer, “Protocol for sorting cells from
mouse brains labeled with mosaic analysis with double markers by flow cytometry,”
STAR Protocols, vol. 5, no. 1. Elsevier, 2023.
ista: Amberg N, Cheung GT, Hippenmeyer S. 2023. Protocol for sorting cells from
mouse brains labeled with mosaic analysis with double markers by flow cytometry.
STAR Protocols. 5(1), 102771.
mla: Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled
with Mosaic Analysis with Double Markers by Flow Cytometry.” STAR Protocols,
vol. 5, no. 1, 102771, Elsevier, 2023, doi:10.1016/j.xpro.2023.102771.
short: N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2023).
date_created: 2023-12-13T11:48:05Z
date_published: 2023-12-08T00:00:00Z
date_updated: 2023-12-18T08:06:14Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.xpro.2023.102771
ec_funded: 1
external_id:
pmid:
- '38070137'
intvolume: ' 5'
issue: '1'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Neuroscience
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.xpro.2023.102771
month: '12'
oa: 1
oa_version: Submitted Version
pmid: 1
project:
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: STAR Protocols
publication_identifier:
issn:
- 2666-1667
publication_status: epub_ahead
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Protocol for sorting cells from mouse brains labeled with mosaic analysis with
double markers by flow cytometry
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2023'
...
---
_id: '12679'
abstract:
- lang: eng
text: How to generate a brain of correct size and with appropriate cell-type diversity
during development is a major question in Neuroscience. In the developing neocortex,
radial glial progenitor (RGP) cells are the main neural stem cells that produce
cortical excitatory projection neurons, glial cells, and establish the prospective
postnatal stem cell niche in the lateral ventricles. RGPs follow a tightly orchestrated
developmental program that when disrupted can result in severe cortical malformations
such as microcephaly and megalencephaly. The precise cellular and molecular mechanisms
instructing faithful RGP lineage progression are however not well understood.
This review will summarize recent conceptual advances that contribute to our understanding
of the general principles of RGP lineage progression.
acknowledgement: "I wish to thank all current and past members of the Hippenmeyer
laboratory at ISTA for exciting discussions on the subject of this review. I apologize
to colleagues whose work I could not cite and/or discuss in the frame of the available
space. Work in the Hippenmeyer laboratory on the\r\ndiscussed topic is supported
by ISTA institutional funds, FWF SFB F78 to S.H., and the European Research Council
(ERC) under the European Union’s Horizon 2020 Research and Innovation Programme
(grant agree-ment no. 725780 LinPro) to SH."
article_number: '102695'
article_processing_charge: Yes (via OA deal)
article_type: review
author:
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: 'Hippenmeyer S. Principles of neural stem cell lineage progression: Insights
from developing cerebral cortex. Current Opinion in Neurobiology. 2023;79(4).
doi:10.1016/j.conb.2023.102695'
apa: 'Hippenmeyer, S. (2023). Principles of neural stem cell lineage progression:
Insights from developing cerebral cortex. Current Opinion in Neurobiology.
Elsevier. https://doi.org/10.1016/j.conb.2023.102695'
chicago: 'Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression:
Insights from Developing Cerebral Cortex.” Current Opinion in Neurobiology.
Elsevier, 2023. https://doi.org/10.1016/j.conb.2023.102695.'
ieee: 'S. Hippenmeyer, “Principles of neural stem cell lineage progression: Insights
from developing cerebral cortex,” Current Opinion in Neurobiology, vol.
79, no. 4. Elsevier, 2023.'
ista: 'Hippenmeyer S. 2023. Principles of neural stem cell lineage progression:
Insights from developing cerebral cortex. Current Opinion in Neurobiology. 79(4),
102695.'
mla: 'Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression: Insights
from Developing Cerebral Cortex.” Current Opinion in Neurobiology, vol.
79, no. 4, 102695, Elsevier, 2023, doi:10.1016/j.conb.2023.102695.'
short: S. Hippenmeyer, Current Opinion in Neurobiology 79 (2023).
date_created: 2023-02-26T12:24:21Z
date_published: 2023-04-01T00:00:00Z
date_updated: 2023-08-16T12:30:25Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.conb.2023.102695
ec_funded: 1
external_id:
isi:
- '000953497700001'
pmid:
- '36842274'
file:
- access_level: open_access
checksum: 4d11c4ca87e6cbc4d2ac46d3225ea615
content_type: application/pdf
creator: dernst
date_created: 2023-08-16T12:29:06Z
date_updated: 2023-08-16T12:29:06Z
file_id: '14071'
file_name: 2023_CurrentOpinionNeurobio_Hippenmeyer.pdf
file_size: 1787894
relation: main_file
success: 1
file_date_updated: 2023-08-16T12:29:06Z
has_accepted_license: '1'
intvolume: ' 79'
isi: 1
issue: '4'
keyword:
- General Neuroscience
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Current Opinion in Neurobiology
publication_identifier:
issn:
- 0959-4388
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Principles of neural stem cell lineage progression: Insights from developing
cerebral cortex'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 79
year: '2023'
...
---
_id: '12802'
abstract:
- lang: eng
text: Little is known about the critical metabolic changes that neural cells have
to undergo during development and how temporary shifts in this program can influence
brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5,
a transporter of metabolically essential large neutral amino acids (LNAAs), lead
to autism, we employed metabolomic profiling to study the metabolic states of
the cerebral cortex across different developmental stages. We found that the forebrain
undergoes significant metabolic remodeling throughout development, with certain
groups of metabolites showing stage-specific changes, but what are the consequences
of perturbing this metabolic program? By manipulating Slc7a5 expression in neural
cells, we found that the metabolism of LNAAs and lipids are interconnected in
the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state,
leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific
alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Freeman and V. Voronin for technical assistance, S. Deixler,
A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal
colony. We thank L. Andersen and J. Sonntag, who were involved in generating the
MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance
with the proteomic analysis, as well as the ISTA electron microscopy and Imaging
and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed
by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge
the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular
metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was
performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated
using Biorender.com. This work was supported by the Austrian Science Fund (FWF,
DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Daniel
full_name: Malzl, Daniel
last_name: Malzl
- first_name: Maria
full_name: Gerykova Bujalkova, Maria
last_name: Gerykova Bujalkova
- first_name: Mateja
full_name: Smogavec, Mateja
last_name: Smogavec
- first_name: Lena A.
full_name: Schwarz, Lena A.
last_name: Schwarz
- first_name: Sarah
full_name: Gorkiewicz, Sarah
id: f141a35d-15a9-11ec-9fb2-fef6becc7b6f
last_name: Gorkiewicz
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Christian
full_name: Knittl-Frank, Christian
last_name: Knittl-Frank
- first_name: Marianna
full_name: Tassinari, Marianna
id: 7af593f1-d44a-11ed-bf94-a3646a6bb35e
last_name: Tassinari
- first_name: Nuno
full_name: Maulide, Nuno
last_name: Maulide
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Jörg
full_name: Menche, Jörg
last_name: Menche
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal
neuronal excitability and survival. Cell. 2023;186(9):1950-1967.e25. doi:10.1016/j.cell.2023.02.037
apa: Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz,
L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal
excitability and survival. Cell. Elsevier. https://doi.org/10.1016/j.cell.2023.02.037
chicago: Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova,
Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino
Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell. Elsevier,
2023. https://doi.org/10.1016/j.cell.2023.02.037.
ieee: L. Knaus et al., “Large neutral amino acid levels tune perinatal neuronal
excitability and survival,” Cell, vol. 186, no. 9. Elsevier, p. 1950–1967.e25,
2023.
ista: Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA,
Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke
T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels
tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.
mla: Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal
Excitability and Survival.” Cell, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25,
doi:10.1016/j.cell.2023.02.037.
short: L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A.
Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N.
Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25.
date_created: 2023-04-05T08:15:40Z
date_published: 2023-04-27T00:00:00Z
date_updated: 2024-02-07T08:03:32Z
day: '27'
ddc:
- '570'
department:
- _id: SiHi
- _id: GaNo
doi: 10.1016/j.cell.2023.02.037
ec_funded: 1
external_id:
isi:
- '000991468700001'
file:
- access_level: open_access
checksum: 47e94fbe19e86505b429cb7a5b503ce6
content_type: application/pdf
creator: dernst
date_created: 2023-05-02T09:26:21Z
date_updated: 2023-05-02T09:26:21Z
file_id: '12889'
file_name: 2023_Cell_Knaus.pdf
file_size: 15712841
relation: main_file
success: 1
file_date_updated: 2023-05-02T09:26:21Z
has_accepted_license: '1'
intvolume: ' 186'
isi: 1
issue: '9'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 1950-1967.e25
project:
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
publication: Cell
publication_identifier:
issn:
- 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/feed-them-or-lose-them/
record:
- id: '13107'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Large neutral amino acid levels tune perinatal neuronal excitability and survival
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 186
year: '2023'
...
---
_id: '11336'
abstract:
- lang: eng
text: The generation of a correctly-sized cerebral cortex with all-embracing neuronal
and glial cell-type diversity critically depends on faithful radial glial progenitor
(RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression
is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity
results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene
expression instructs RGP lineage progression is unknown. Here we utilize Mosaic
Analysis with Double Markers (MADM)-based single cell technology and demonstrate
that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts
at the global tissue-wide level. Conversely, cortical astrocyte production and
maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation.
We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression
that are dependent on complex interplays between intrinsic and tissue-wide properties.
In a broader context our results imply a critical role for the genetic and cellular
niche environment in neural stem cell behavior.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit) and S. Gharagozlou for technical support. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics
Facility (IOF), Lab Support Facility (LSF), and Preclinical Facility (PCF). N.A.
received funding from the FWF Firnberg-Programm (T 1031). The work was supported by IST institutional funds and by the European Research Council (ERC) under the European Union’s Horizon
2020 research and innovation program (grant agreement 725780 LinPro) to S.H.
article_number: abq1263
article_processing_charge: No
article_type: original
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Amberg N, Pauler F, Streicher C, Hippenmeyer S. Tissue-wide genetic and cellular
landscape shapes the execution of sequential PRC2 functions in neural stem cell
lineage progression. Science Advances. 2022;8(44). doi:10.1126/sciadv.abq1263
apa: Amberg, N., Pauler, F., Streicher, C., & Hippenmeyer, S. (2022). Tissue-wide
genetic and cellular landscape shapes the execution of sequential PRC2 functions
in neural stem cell lineage progression. Science Advances. American Association
for the Advancement of Science. https://doi.org/10.1126/sciadv.abq1263
chicago: Amberg, Nicole, Florian Pauler, Carmen Streicher, and Simon Hippenmeyer.
“Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential
PRC2 Functions in Neural Stem Cell Lineage Progression.” Science Advances.
American Association for the Advancement of Science, 2022. https://doi.org/10.1126/sciadv.abq1263.
ieee: N. Amberg, F. Pauler, C. Streicher, and S. Hippenmeyer, “Tissue-wide genetic
and cellular landscape shapes the execution of sequential PRC2 functions in neural
stem cell lineage progression,” Science Advances, vol. 8, no. 44. American
Association for the Advancement of Science, 2022.
ista: Amberg N, Pauler F, Streicher C, Hippenmeyer S. 2022. Tissue-wide genetic
and cellular landscape shapes the execution of sequential PRC2 functions in neural
stem cell lineage progression. Science Advances. 8(44), abq1263.
mla: Amberg, Nicole, et al. “Tissue-Wide Genetic and Cellular Landscape Shapes the
Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.”
Science Advances, vol. 8, no. 44, abq1263, American Association for the
Advancement of Science, 2022, doi:10.1126/sciadv.abq1263.
short: N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022).
date_created: 2022-04-26T15:04:50Z
date_published: 2022-11-01T00:00:00Z
date_updated: 2023-05-31T12:24:10Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1126/sciadv.abq1263
ec_funded: 1
file:
- access_level: open_access
checksum: 0117023e188542082ca6693cf39e7f03
content_type: application/pdf
creator: patrickd
date_created: 2023-03-21T14:18:10Z
date_updated: 2023-03-21T14:18:10Z
file_id: '12742'
file_name: sciadv.abq1263.pdf
file_size: 2973998
relation: main_file
success: 1
file_date_updated: 2023-03-21T14:18:10Z
has_accepted_license: '1'
intvolume: ' 8'
issue: '44'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
publication: Science Advances
publication_identifier:
issn:
- 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/
scopus_import: '1'
status: public
title: Tissue-wide genetic and cellular landscape shapes the execution of sequential
PRC2 functions in neural stem cell lineage progression
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 8
year: '2022'
...
---
_id: '11449'
abstract:
- lang: eng
text: Mutations are acquired frequently, such that each cell's genome inscribes
its history of cell divisions. Common genomic alterations involve loss of heterozygosity
(LOH). LOH accumulates throughout the genome, offering large encoding capacity
for inferring cell lineage. Using only single-cell RNA sequencing (scRNA-seq)
of mouse brain cells, we found that LOH events spanning multiple genes are revealed
as tracts of monoallelically expressed, constitutionally heterozygous single-nucleotide
variants (SNVs). We simultaneously inferred cell lineage and marked developmental
time points based on X chromosome inactivation and the total number of LOH events
while identifying cell types from gene expression patterns. Our results are consistent
with progenitor cells giving rise to multiple cortical cell types through stereotyped
expansion and distinct waves of neurogenesis. This type of retrospective analysis
could be incorporated into scRNA-seq pipelines and, compared with experimental
approaches for determining lineage in model organisms, is applicable where genetic
engineering is prohibited, such as humans.
acknowledgement: D.J.A. thanks Wayne K. Potts, Alan R. Rogers, Kristen Hawkes, Ryk
Ward, and Jon Seger for inspiring a young undergraduate to apply evolutionary theory
to intraorganism development. Supported by the Paul G. Allen Frontiers Group (University
of Washington); NIH R00HG010152 (Dartmouth); and NÖ Forschung und Bildung n[f+b]
life science call grant (C13-002) and the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation program 725780 LinPro
to S.H.
article_processing_charge: No
article_type: original
author:
- first_name: Donovan J.
full_name: Anderson, Donovan J.
last_name: Anderson
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
- first_name: Aaron
full_name: Mckenna, Aaron
last_name: Mckenna
- first_name: Jay
full_name: Shendure, Jay
last_name: Shendure
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Marshall S.
full_name: Horwitz, Marshall S.
last_name: Horwitz
citation:
ama: Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous
brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical
development. Cell Systems. 2022;13(6):438-453.e5. doi:10.1016/j.cels.2022.03.006
apa: Anderson, D. J., Pauler, F., Mckenna, A., Shendure, J., Hippenmeyer, S., &
Horwitz, M. S. (2022). Simultaneous brain cell type and lineage determined by
scRNA-seq reveals stereotyped cortical development. Cell Systems. Elsevier.
https://doi.org/10.1016/j.cels.2022.03.006
chicago: Anderson, Donovan J., Florian Pauler, Aaron Mckenna, Jay Shendure, Simon
Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Brain Cell Type and Lineage
Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems.
Elsevier, 2022. https://doi.org/10.1016/j.cels.2022.03.006.
ieee: D. J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, and M.
S. Horwitz, “Simultaneous brain cell type and lineage determined by scRNA-seq
reveals stereotyped cortical development,” Cell Systems, vol. 13, no. 6.
Elsevier, p. 438–453.e5, 2022.
ista: Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. 2022.
Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped
cortical development. Cell Systems. 13(6), 438–453.e5.
mla: Anderson, Donovan J., et al. “Simultaneous Brain Cell Type and Lineage Determined
by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems, vol.
13, no. 6, Elsevier, 2022, p. 438–453.e5, doi:10.1016/j.cels.2022.03.006.
short: D.J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz,
Cell Systems 13 (2022) 438–453.e5.
date_created: 2022-06-19T22:01:57Z
date_published: 2022-06-15T00:00:00Z
date_updated: 2023-08-03T07:19:43Z
day: '15'
department:
- _id: SiHi
doi: 10.1016/j.cels.2022.03.006
ec_funded: 1
external_id:
isi:
- '000814124400002'
pmid:
- '35452605'
intvolume: ' 13'
isi: 1
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.cels.2022.03.006
month: '06'
oa: 1
oa_version: Published Version
page: 438-453.e5
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
publication: Cell Systems
publication_identifier:
eissn:
- 2405-4720
issn:
- 2405-4712
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped
cortical development
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2022'
...
---
_id: '8544'
abstract:
- lang: eng
text: The synaptotrophic hypothesis posits that synapse formation stabilizes dendritic
branches, yet this hypothesis has not been causally tested in vivo in the mammalian
brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2
mediate synaptogenesis between granule cells and Purkinje cells in the molecular
layer of the cerebellar cortex. Here we show that sparse but not global knockout
of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular
layer and overelaboration in the superficial molecular layer. Developmental, overexpression,
structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis
defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner.
A generative model of dendritic growth based on competitive synaptogenesis largely
recapitulates GluD2 sparse and global knockout phenotypes. Our results support
the synaptotrophic hypothesis at initial stages of dendrite development, suggest
a second mode in which cumulative synapse formation inhibits further dendrite
growth, and highlight the importance of competition in dendrite morphogenesis.
acknowledgement: We thank M. Mishina for GluD2fl frozen embryos, T.C. Südhof and J.I.
Morgan for Cbln1fl mice, L. Anderson for help in generating the MADM alleles, W.
Joo for a previously unpublished construct, M. Yuzaki, K. Shen, J. Ding, and members
of the Luo lab, including J.M. Kebschull, H. Li, J. Li, T. Li, C.M. McLaughlin,
D. Pederick, J. Ren, D.C. Wang and C. Xu for discussions and critiques of the manuscript,
and M. Yuzaki for supporting Y.H.T. during the final phase of this project. Y.H.T.
was supported by a JSPS fellowship; S.A.S. was supported by a Stanford Graduate
Fellowship and an NSF Predoctoral Fellowship; L.J. is supported by a Stanford Graduate
Fellowship and an NSF Predoctoral Fellowship; M.J.W. is supported by a Burroughs
Wellcome Fund CASI Award. This work was supported by an NIH grant (R01-NS050538)
to L.L.; the European Research Council (ERC) under the European Union's Horizon
2020 research and innovations programme (No. 725780 LinPro) to S.H.; and Simons
and James S. McDonnell Foundations and an NSF CAREER award to S.G.; L.L. is an HHMI
investigator.
article_processing_charge: No
article_type: original
author:
- first_name: Yukari H.
full_name: Takeo, Yukari H.
last_name: Takeo
- first_name: S. Andrew
full_name: Shuster, S. Andrew
last_name: Shuster
- first_name: Linnie
full_name: Jiang, Linnie
last_name: Jiang
- first_name: Miley
full_name: Hu, Miley
last_name: Hu
- first_name: David J.
full_name: Luginbuhl, David J.
last_name: Luginbuhl
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Mark J.
full_name: Wagner, Mark J.
last_name: Wagner
- first_name: Surya
full_name: Ganguli, Surya
last_name: Ganguli
- first_name: Liqun
full_name: Luo, Liqun
last_name: Luo
citation:
ama: Takeo YH, Shuster SA, Jiang L, et al. GluD2- and Cbln1-mediated competitive
synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. Neuron.
2021;109(4):P629-644.E8. doi:10.1016/j.neuron.2020.11.028
apa: Takeo, Y. H., Shuster, S. A., Jiang, L., Hu, M., Luginbuhl, D. J., Rülicke,
T., … Luo, L. (2021). GluD2- and Cbln1-mediated competitive synaptogenesis shapes
the dendritic arbors of cerebellar Purkinje cells. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.11.028
chicago: Takeo, Yukari H., S. Andrew Shuster, Linnie Jiang, Miley Hu, David J. Luginbuhl,
Thomas Rülicke, Ximena Contreras, et al. “GluD2- and Cbln1-Mediated Competitive
Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” Neuron.
Elsevier, 2021. https://doi.org/10.1016/j.neuron.2020.11.028.
ieee: Y. H. Takeo et al., “GluD2- and Cbln1-mediated competitive synaptogenesis
shapes the dendritic arbors of cerebellar Purkinje cells,” Neuron, vol.
109, no. 4. Elsevier, p. P629–644.E8, 2021.
ista: Takeo YH, Shuster SA, Jiang L, Hu M, Luginbuhl DJ, Rülicke T, Contreras X,
Hippenmeyer S, Wagner MJ, Ganguli S, Luo L. 2021. GluD2- and Cbln1-mediated competitive
synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. Neuron.
109(4), P629–644.E8.
mla: Takeo, Yukari H., et al. “GluD2- and Cbln1-Mediated Competitive Synaptogenesis
Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” Neuron, vol.
109, no. 4, Elsevier, 2021, p. P629–644.E8, doi:10.1016/j.neuron.2020.11.028.
short: Y.H. Takeo, S.A. Shuster, L. Jiang, M. Hu, D.J. Luginbuhl, T. Rülicke, X.
Contreras, S. Hippenmeyer, M.J. Wagner, S. Ganguli, L. Luo, Neuron 109 (2021)
P629–644.E8.
date_created: 2020-09-21T11:59:47Z
date_published: 2021-02-17T00:00:00Z
date_updated: 2024-03-06T12:12:48Z
day: '17'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2020.11.028
ec_funded: 1
intvolume: ' 109'
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.06.14.151258
month: '02'
oa: 1
oa_version: Preprint
page: P629-644.E8
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Neuron
publication_identifier:
eissn:
- 1097-4199
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors
of cerebellar Purkinje cells
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 109
year: '2021'
...
---
_id: '8546'
abstract:
- lang: eng
text: Brain neurons arise from relatively few progenitors generating an enormous
diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain
neurogenesis is thought to be that excitatory and inhibitory neurons derive from
separate, spatially segregated progenitors. Whether bi-potential progenitors with
an intrinsic capacity to generate both lineages exist and how such a fate decision
may be regulated are unknown. Using cerebellar development as a model, we discover
that individual progenitors can give rise to both inhibitory and excitatory lineages.
Gradations of Notch activity determine the fates of the progenitors and their
daughters. Daughters with the highest levels of Notch activity retain the progenitor
fate, while intermediate levels of Notch activity generate inhibitory neurons,
and daughters with very low levels of Notch signaling adopt the excitatory fate.
Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating
the ratio of excitatory to inhibitory neurons from common progenitors.
acknowledgement: This work was supported by the program “Investissements d’avenir”
ANR-10-IAIHU-06 , ICM , a Sorbonne Université Emergence grant, an Allen Distinguished
Investigator Award , and the Roger De Spoelberch Foundation Prize (to B.A.H.); Armenise-Harvard
Foundation , AIRC , and CARITRO (to L.T.); and the European Research Council under
the European Union’s Horizon 2020 research and innovation programme grant agreement
no. 725780 LinPro (to S.H.). T.Z. and T.L. were supported by doctoral fellowships
from the China Scholarship Council and A.H.H. by a doctoral DOC fellowship of the
Austrian Academy of Sciences ( 24812 ). All animal work was conducted at the PHENO-ICMice
facility. The Core is supported by 2 “Investissements d’avenir” (ANR-10- IAIHU-06
and ANR-11-INBS-0011-NeurATRIS) and the “Fondation pour la Recherche Médicale.”
Light microscopy work was carried out at ICM’s imaging core facility, ICM.Quant,
and analysis of scRNA-seq data was carried out at ICM’s bioinformatics core facility,
iCONICS. We thank Paulina Ejsmont, Natalia Danda, and Nathalie De Geest for technical
support. We are grateful to Dr. Shahragim TAJBAKHSH for providing R26Rstop-NICD-nGFP
transgenic mice, Dr. Bart De Strooper for Psn1-deficient mice, Dr. Jean-Christophe
Marine for Gt(ROSA)26SortdTom reporter mice, and Dr. Martinez Barbera for Sox2CreERT2
mice. We also give thanks to Dr. Mikio Hoshino for providing Atoh1 and Ptf1a antibodies.
B.A.H. is an Einstein Visiting Fellow of the Berlin Institute of Health .
article_number: '109208'
article_processing_charge: No
article_type: original
author:
- first_name: Tingting
full_name: Zhang, Tingting
last_name: Zhang
- first_name: Tengyuan
full_name: Liu, Tengyuan
last_name: Liu
- first_name: Natalia
full_name: Mora, Natalia
last_name: Mora
- first_name: Justine
full_name: Guegan, Justine
last_name: Guegan
- first_name: Mathilde
full_name: Bertrand, Mathilde
last_name: Bertrand
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Marica
full_name: Anderle, Marica
last_name: Anderle
- first_name: Natasha
full_name: Danda, Natasha
last_name: Danda
- first_name: Luca
full_name: Tiberi, Luca
last_name: Tiberi
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Bassem A.
full_name: Hassan, Bassem A.
last_name: Hassan
citation:
ama: Zhang T, Liu T, Mora N, et al. Generation of excitatory and inhibitory neurons
from common progenitors via Notch signaling in the cerebellum. Cell Reports.
2021;35(10). doi:10.1016/j.celrep.2021.109208
apa: Zhang, T., Liu, T., Mora, N., Guegan, J., Bertrand, M., Contreras, X., … Hassan,
B. A. (2021). Generation of excitatory and inhibitory neurons from common progenitors
via Notch signaling in the cerebellum. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2021.109208
chicago: Zhang, Tingting, Tengyuan Liu, Natalia Mora, Justine Guegan, Mathilde Bertrand,
Ximena Contreras, Andi H Hansen, et al. “Generation of Excitatory and Inhibitory
Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” Cell
Reports. Elsevier, 2021. https://doi.org/10.1016/j.celrep.2021.109208.
ieee: T. Zhang et al., “Generation of excitatory and inhibitory neurons from
common progenitors via Notch signaling in the cerebellum,” Cell Reports,
vol. 35, no. 10. Elsevier, 2021.
ista: Zhang T, Liu T, Mora N, Guegan J, Bertrand M, Contreras X, Hansen AH, Streicher
C, Anderle M, Danda N, Tiberi L, Hippenmeyer S, Hassan BA. 2021. Generation of
excitatory and inhibitory neurons from common progenitors via Notch signaling
in the cerebellum. Cell Reports. 35(10), 109208.
mla: Zhang, Tingting, et al. “Generation of Excitatory and Inhibitory Neurons from
Common Progenitors via Notch Signaling in the Cerebellum.” Cell Reports,
vol. 35, no. 10, 109208, Elsevier, 2021, doi:10.1016/j.celrep.2021.109208.
short: T. Zhang, T. Liu, N. Mora, J. Guegan, M. Bertrand, X. Contreras, A.H. Hansen,
C. Streicher, M. Anderle, N. Danda, L. Tiberi, S. Hippenmeyer, B.A. Hassan, Cell
Reports 35 (2021).
date_created: 2020-09-21T12:00:48Z
date_published: 2021-06-08T00:00:00Z
date_updated: 2023-08-04T11:00:48Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.celrep.2021.109208
ec_funded: 1
external_id:
isi:
- '000659894300001'
pmid:
- '34107249 '
file:
- access_level: open_access
checksum: 7def3d42ebc8f5675efb6f38819e3e2e
content_type: application/pdf
creator: cziletti
date_created: 2021-06-15T14:01:35Z
date_updated: 2021-06-15T14:01:35Z
file_id: '9554'
file_name: 2021_CellReports_Zhang.pdf
file_size: 8900385
relation: main_file
success: 1
file_date_updated: 2021-06-15T14:01:35Z
has_accepted_license: '1'
intvolume: ' 35'
isi: 1
issue: '10'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
publication: Cell Reports
publication_identifier:
eissn:
- ' 22111247'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- relation: earlier_version
url: https://doi.org/10.1101/2020.03.18.997205
scopus_import: '1'
status: public
title: Generation of excitatory and inhibitory neurons from common progenitors via
Notch signaling in the cerebellum
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 35
year: '2021'
...
---
_id: '9073'
abstract:
- lang: eng
text: The sensory and cognitive abilities of the mammalian neocortex are underpinned
by intricate columnar and laminar circuits formed from an array of diverse neuronal
populations. One approach to determining how interactions between these circuit
components give rise to complex behavior is to investigate the rules by which
cortical circuits are formed and acquire functionality during development. This
review summarizes recent research on the development of the neocortex, from genetic
determination in neural stem cells through to the dynamic role that specific neuronal
populations play in the earliest circuits of neocortex, and how they contribute
to emergent function and cognition. While many of these endeavors take advantage
of model systems, consideration will also be given to advances in our understanding
of activity in nascent human circuits. Such cross-species perspective is imperative
when investigating the mechanisms underlying the dysfunction of early neocortical
circuits in neurodevelopmental disorders, so that one can identify targets amenable
to therapeutic intervention.
acknowledgement: Work in the I.L.H.-O. laboratory was supported by European Research
Council Grant ERC-2015-CoG 681577 and German Research Foundation Ha 4466/10-1, Ha4466/11-1,
Ha4466/12-1, SPP 1665, and SFB 936B5. Work in the S.J.B.B. laboratory was supported
by Biotechnology and Biological Sciences Research Council BB/P003796/1, Medical
Research Council MR/K004387/1 and MR/T033320/1, Wellcome Trust 215199/Z/19/Z and
102386/Z/13/Z, and John Fell Fund. Work in the S.H. laboratory was supported by
European Research Council Grants ERC-2016-CoG 725780 LinPro and FWF SFB F78. This
work was supported by National Institutes of Health Grant NIMH 1R01MH110553 to N.V.D.M.G.
Work in the J.A.C. laboratory was supported by the Ludwig Family Foundation, Simons
Foundation SFARI Research Award, and National Institutes of Health/National Institute
of Mental Health R01 MH102365 and R01MH113852. The B.V. laboratory was supported
by Whitehall Foundation 2017-12-73, National Science Foundation 1736028, National
Institutes of Health, National Institute of General Medical Sciences R01GM134363-01,
and Halıcıoğlu Data Science Institute Fellowship. This work was supported by the
University of California San Diego School of Medicine.
article_processing_charge: No
article_type: original
author:
- first_name: Ileana L.
full_name: Hanganu-Opatz, Ileana L.
last_name: Hanganu-Opatz
- first_name: Simon J. B.
full_name: Butt, Simon J. B.
last_name: Butt
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Natalia V.
full_name: De Marco García, Natalia V.
last_name: De Marco García
- first_name: Jessica A.
full_name: Cardin, Jessica A.
last_name: Cardin
- first_name: Bradley
full_name: Voytek, Bradley
last_name: Voytek
- first_name: Alysson R.
full_name: Muotri, Alysson R.
last_name: Muotri
citation:
ama: Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, et al. The logic of developing neocortical
circuits in health and disease. The Journal of Neuroscience. 2021;41(5):813-822.
doi:10.1523/jneurosci.1655-20.2020
apa: Hanganu-Opatz, I. L., Butt, S. J. B., Hippenmeyer, S., De Marco García, N.
V., Cardin, J. A., Voytek, B., & Muotri, A. R. (2021). The logic of developing
neocortical circuits in health and disease. The Journal of Neuroscience.
Society for Neuroscience. https://doi.org/10.1523/jneurosci.1655-20.2020
chicago: Hanganu-Opatz, Ileana L., Simon J. B. Butt, Simon Hippenmeyer, Natalia
V. De Marco García, Jessica A. Cardin, Bradley Voytek, and Alysson R. Muotri.
“The Logic of Developing Neocortical Circuits in Health and Disease.” The Journal
of Neuroscience. Society for Neuroscience, 2021. https://doi.org/10.1523/jneurosci.1655-20.2020.
ieee: I. L. Hanganu-Opatz et al., “The logic of developing neocortical circuits
in health and disease,” The Journal of Neuroscience, vol. 41, no. 5. Society
for Neuroscience, pp. 813–822, 2021.
ista: Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, De Marco García NV, Cardin JA,
Voytek B, Muotri AR. 2021. The logic of developing neocortical circuits in health
and disease. The Journal of Neuroscience. 41(5), 813–822.
mla: Hanganu-Opatz, Ileana L., et al. “The Logic of Developing Neocortical Circuits
in Health and Disease.” The Journal of Neuroscience, vol. 41, no. 5, Society
for Neuroscience, 2021, pp. 813–22, doi:10.1523/jneurosci.1655-20.2020.
short: I.L. Hanganu-Opatz, S.J.B. Butt, S. Hippenmeyer, N.V. De Marco García, J.A.
Cardin, B. Voytek, A.R. Muotri, The Journal of Neuroscience 41 (2021) 813–822.
date_created: 2021-02-03T12:23:51Z
date_published: 2021-02-03T00:00:00Z
date_updated: 2023-09-05T14:03:17Z
day: '03'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1523/jneurosci.1655-20.2020
ec_funded: 1
external_id:
isi:
- '000616763400002'
pmid:
- '33431633'
file:
- access_level: open_access
checksum: 578fd7ed1a0aef74bce61bea2d987b33
content_type: application/pdf
creator: dernst
date_created: 2022-05-27T06:59:55Z
date_updated: 2022-05-27T06:59:55Z
file_id: '11414'
file_name: 2021_JourNeuroscience_Hanganu.pdf
file_size: 1031150
relation: main_file
success: 1
file_date_updated: 2022-05-27T06:59:55Z
has_accepted_license: '1'
intvolume: ' 41'
isi: 1
issue: '5'
keyword:
- General Neuroscience
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 813-822
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
publication: The Journal of Neuroscience
publication_identifier:
eissn:
- 1529-2401
issn:
- 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: The logic of developing neocortical circuits in health and disease
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 41
year: '2021'
...
---
_id: '9082'
abstract:
- lang: eng
text: Acquired mutations are sufficiently frequent such that the genome of a single
cell offers a record of its history of cell divisions. Among more common somatic
genomic alterations are loss of heterozygosity (LOH). Large LOH events are potentially
detectable in single cell RNA sequencing (scRNA-seq) datasets as tracts of monoallelic
expression for constitutionally heterozygous single nucleotide variants (SNVs)
located among contiguous genes. We identified runs of monoallelic expression,
consistent with LOH, uniquely distributed throughout the genome in single cell
brain cortex transcriptomes of F1 hybrids involving different inbred mouse strains.
We then phylogenetically reconstructed single cell lineages and simultaneously
identified cell types by corresponding gene expression patterns. Our results are
consistent with progenitor cells giving rise to multiple cortical cell types through
stereotyped expansion and distinct waves of neurogenesis. Compared to engineered
recording systems, LOH events accumulate throughout the genome and across the
lifetime of an organism, affording tremendous capacity for encoding lineage information
and increasing resolution for later cell divisions. This approach can conceivably
be computationally incorporated into scRNA-seq analysis and may be useful for
organisms where genetic engineering is prohibitive, such as humans.
acknowledgement: "We thank Bill Bolosky, Microsoft Research, for earlier work showing
proof of concept in TCGA\r\nbulk RNA-seq data. Supported by the Paul G. Allen Frontiers
Group (University of Washington);\r\nNIH R00HG010152 (Dartmouth); and NÖ Forschung
und Bildung n[f+b] life science call grant\r\n(C13-002) to SH, and the European
Research Council (ERC) under the European Union’s\r\nHorizon 2020 research and innovation
program 725780 LinPro to SH."
article_processing_charge: No
author:
- first_name: Donovan J.
full_name: Anderson, Donovan J.
last_name: Anderson
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
- first_name: Aaron
full_name: McKenna, Aaron
last_name: McKenna
- first_name: Jay
full_name: Shendure, Jay
last_name: Shendure
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Marshall S.
full_name: Horwitz, Marshall S.
last_name: Horwitz
citation:
ama: Anderson DJ, Pauler F, McKenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous
identification of brain cell type and lineage via single cell RNA sequencing.
bioRxiv. doi:10.1101/2020.12.31.425016
apa: Anderson, D. J., Pauler, F., McKenna, A., Shendure, J., Hippenmeyer, S., &
Horwitz, M. S. (n.d.). Simultaneous identification of brain cell type and lineage
via single cell RNA sequencing. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2020.12.31.425016
chicago: Anderson, Donovan J., Florian Pauler, Aaron McKenna, Jay Shendure, Simon
Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Identification of Brain Cell
Type and Lineage via Single Cell RNA Sequencing.” BioRxiv. Cold Spring
Harbor Laboratory, n.d. https://doi.org/10.1101/2020.12.31.425016.
ieee: D. J. Anderson, F. Pauler, A. McKenna, J. Shendure, S. Hippenmeyer, and M.
S. Horwitz, “Simultaneous identification of brain cell type and lineage via single
cell RNA sequencing,” bioRxiv. Cold Spring Harbor Laboratory.
ista: Anderson DJ, Pauler F, McKenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous
identification of brain cell type and lineage via single cell RNA sequencing.
bioRxiv, 10.1101/2020.12.31.425016.
mla: Anderson, Donovan J., et al. “Simultaneous Identification of Brain Cell Type
and Lineage via Single Cell RNA Sequencing.” BioRxiv, Cold Spring Harbor
Laboratory, doi:10.1101/2020.12.31.425016.
short: D.J. Anderson, F. Pauler, A. McKenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz,
BioRxiv (n.d.).
date_created: 2021-02-04T07:23:23Z
date_published: 2021-01-01T00:00:00Z
date_updated: 2021-02-04T07:29:53Z
day: '01'
department:
- _id: SiHi
doi: 10.1101/2020.12.31.425016
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.12.31.425016
month: '01'
oa: 1
oa_version: Preprint
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
status: public
title: Simultaneous identification of brain cell type and lineage via single cell
RNA sequencing
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2021'
...
---
_id: '9188'
abstract:
- lang: eng
text: Genomic imprinting is an epigenetic mechanism that results in parental allele-specific
expression of ~1% of all genes in mouse and human. Imprinted genes are key developmental
regulators and play pivotal roles in many biological processes such as nutrient
transfer from the mother to offspring and neuronal development. Imprinted genes
are also involved in human disease, including neurodevelopmental disorders, and
often occur in clusters that are regulated by a common imprint control region
(ICR). In extra-embryonic tissues ICRs can act over large distances, with the
largest surrounding Igf2r spanning over 10 million base-pairs. Besides classical
imprinted expression that shows near exclusive maternal or paternal expression,
widespread biased imprinted expression has been identified mainly in brain. In
this review we discuss recent developments mapping cell type specific imprinted
expression in extra-embryonic tissues and neocortex in the mouse. We highlight
the advantages of using an inducible uniparental chromosome disomy (UPD) system
to generate cells carrying either two maternal or two paternal copies of a specific
chromosome to analyze the functional consequences of genomic imprinting. Mosaic
Analysis with Double Markers (MADM) allows fluorescent labeling and concomitant
induction of UPD sparsely in specific cell types, and thus to over-express or
suppress all imprinted genes on that chromosome. To illustrate the utility of
this technique, we explain how MADM-induced UPD revealed new insights about the
function of the well-studied Cdkn1c imprinted gene, and how MADM-induced UPDs
led to identification of highly cell type specific phenotypes related to perturbed
imprinted expression in the mouse neocortex. Finally, we give an outlook on how
MADM could be used to probe cell type specific imprinted expression in other tissues
in mouse, particularly in extra-embryonic tissues.
acknowledgement: We thank Melissa Stouffer for critically reading the manuscript.
This work was supported by IST Austria institutional funds; NÖ Forschung und Bildung
n[f + b] life science call grant (C13-002) to S.H. and the European Research Council
(ERC) under the European Union's Horizon 2020 research and innovation program (grant
agreement 725780 LinPro) to S.H.
article_number: '104986'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
- first_name: Quanah
full_name: Hudson, Quanah
last_name: Hudson
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. Inducible uniparental chromosome
disomy to probe genomic imprinting at single-cell level in brain and beyond. Neurochemistry
International. 2021;145(5). doi:10.1016/j.neuint.2021.104986
apa: Pauler, F., Hudson, Q., Laukoter, S., & Hippenmeyer, S. (2021). Inducible
uniparental chromosome disomy to probe genomic imprinting at single-cell level
in brain and beyond. Neurochemistry International. Elsevier. https://doi.org/10.1016/j.neuint.2021.104986
chicago: Pauler, Florian, Quanah Hudson, Susanne Laukoter, and Simon Hippenmeyer.
“Inducible Uniparental Chromosome Disomy to Probe Genomic Imprinting at Single-Cell
Level in Brain and Beyond.” Neurochemistry International. Elsevier, 2021.
https://doi.org/10.1016/j.neuint.2021.104986.
ieee: F. Pauler, Q. Hudson, S. Laukoter, and S. Hippenmeyer, “Inducible uniparental
chromosome disomy to probe genomic imprinting at single-cell level in brain and
beyond,” Neurochemistry International, vol. 145, no. 5. Elsevier, 2021.
ista: Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. 2021. Inducible uniparental
chromosome disomy to probe genomic imprinting at single-cell level in brain and
beyond. Neurochemistry International. 145(5), 104986.
mla: Pauler, Florian, et al. “Inducible Uniparental Chromosome Disomy to Probe Genomic
Imprinting at Single-Cell Level in Brain and Beyond.” Neurochemistry International,
vol. 145, no. 5, 104986, Elsevier, 2021, doi:10.1016/j.neuint.2021.104986.
short: F. Pauler, Q. Hudson, S. Laukoter, S. Hippenmeyer, Neurochemistry International
145 (2021).
date_created: 2021-02-23T12:31:43Z
date_published: 2021-05-01T00:00:00Z
date_updated: 2023-08-07T13:48:26Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.neuint.2021.104986
ec_funded: 1
external_id:
isi:
- '000635575000005'
pmid:
- '33600873'
file:
- access_level: open_access
checksum: c6d7a40089cd29e289f9b22e75768304
content_type: application/pdf
creator: kschuh
date_created: 2021-08-11T12:30:38Z
date_updated: 2021-08-11T12:30:38Z
file_id: '9883'
file_name: 2021_NCI_Pauler.pdf
file_size: 7083499
relation: main_file
success: 1
file_date_updated: 2021-08-11T12:30:38Z
has_accepted_license: '1'
intvolume: ' 145'
isi: 1
issue: '5'
keyword:
- Cell Biology
- Cellular and Molecular Neuroscience
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
publication: Neurochemistry International
publication_identifier:
issn:
- 0197-0186
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell
level in brain and beyond
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 145
year: '2021'
...
---
_id: '9603'
abstract:
- lang: eng
text: Mosaic analysis with double markers (MADM) offers one approach to visualize
and concomitantly manipulate genetically defined cells in mice with single-cell
resolution. MADM applications include the analysis of lineage, single-cell morphology
and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous
gene functions in vivo in health and disease. Yet, MADM can only be applied to
<25% of all mouse genes on select chromosomes to date. To overcome this limitation,
we generate transgenic mice with knocked-in MADM cassettes near the centromeres
of all 19 autosomes and validate their use across organs. With this resource,
>96% of the entire mouse genome can now be subjected to single-cell genetic mosaic
analysis. Beyond a proof of principle, we apply our MADM library to systematically
trace sister chromatid segregation in distinct mitotic cell lineages. We find
striking chromosome-specific biases in segregation patterns, reflecting a putative
mechanism for the asymmetric segregation of genetic determinants in somatic stem
cell division.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank the Bioimaging, Life Science, and Pre-Clinical Facilities
at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain,
M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance;
R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of
the Hippenmeyer lab for discussion. This work was supported by National Institutes
of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator
of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is
a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This
work also received support from IST Austria institutional funds , FWF SFB F78 to
S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh
Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H.,
and the European Research Council (ERC) under the European Union’s Horizon 2020
Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.
article_number: '109274'
article_processing_charge: No
article_type: original
author:
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Amarbayasgalan
full_name: Davaatseren, Amarbayasgalan
id: 70ADC922-B424-11E9-99E3-BA18E6697425
last_name: Davaatseren
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Johanna
full_name: Sonntag, Johanna
id: 32FE7D7C-F248-11E8-B48F-1D18A9856A87
last_name: Sonntag
- first_name: Lill
full_name: Andersen, Lill
last_name: Andersen
- first_name: Tina
full_name: Bernthaler, Tina
last_name: Bernthaler
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Anna-Magdalena
full_name: Heger, Anna-Magdalena
id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
last_name: Heger
- first_name: Randy L.
full_name: Johnson, Randy L.
last_name: Johnson
- first_name: Lindsay A.
full_name: Schwarz, Lindsay A.
last_name: Schwarz
- first_name: Liqun
full_name: Luo, Liqun
last_name: Luo
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM
mice for single-cell genetic mosaic analysis. Cell Reports. 2021;35(12).
doi:10.1016/j.celrep.2021.109274
apa: Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen,
L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell
genetic mosaic analysis. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2021.109274
chicago: Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen,
Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library
of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports. Cell
Press, 2021. https://doi.org/10.1016/j.celrep.2021.109274.
ieee: X. Contreras et al., “A genome-wide library of MADM mice for single-cell
genetic mosaic analysis,” Cell Reports, vol. 35, no. 12. Cell Press, 2021.
ista: Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler
T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer
S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis.
Cell Reports. 35(12), 109274.
mla: Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell
Genetic Mosaic Analysis.” Cell Reports, vol. 35, no. 12, 109274, Cell Press,
2021, doi:10.1016/j.celrep.2021.109274.
short: X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen,
T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo,
T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).
date_created: 2021-06-27T22:01:48Z
date_published: 2021-06-22T00:00:00Z
date_updated: 2023-08-10T13:55:00Z
day: '22'
ddc:
- '570'
department:
- _id: SiHi
- _id: LoSw
- _id: PreCl
doi: 10.1016/j.celrep.2021.109274
ec_funded: 1
external_id:
isi:
- '000664463600016'
file:
- access_level: open_access
checksum: d49520fdcbbb5c2f883bddb67cee5d77
content_type: application/pdf
creator: asandaue
date_created: 2021-06-28T14:06:24Z
date_updated: 2021-06-28T14:06:24Z
file_id: '9613'
file_name: 2021_CellReports_Contreras.pdf
file_size: 7653149
relation: main_file
success: 1
file_date_updated: 2021-06-28T14:06:24Z
has_accepted_license: '1'
intvolume: ' 35'
isi: 1
issue: '12'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Cell Reports
publication_identifier:
eissn:
- '22111247'
publication_status: published
publisher: Cell Press
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/
scopus_import: '1'
status: public
title: A genome-wide library of MADM mice for single-cell genetic mosaic analysis
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 35
year: '2021'
...
---
_id: '10321'
abstract:
- lang: eng
text: Mosaic analysis with double markers (MADM) technology enables the generation
of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling
and introduction of a mutation of a gene of interest with single-cell resolution.
This protocol highlights major steps for the generation of genetic mosaic tissue
and the isolation and processing of respective tissues for downstream histological
analysis. For complete details on the use and execution of this protocol, please
refer to Contreras et al. (2021).
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: This research was supported by the Scientific Service Units (SSU)
at IST Austria through resources provided by the Bioimaging (BIF) and Preclinical
Facilities (PCF). We particularly thank Mohammad Goudarzi for assistance with photography
of mouse perfusion and dissection. N.A. received support from FWF Firnberg-Programm
(T 1031). This work was also supported by IST Austria institutional funds; FWF SFB
F78 to S.H.; and the European Research Council (ERC) under the European Union’s
Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro)
to S.H.
article_number: '100939'
article_processing_charge: Yes
article_type: original
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Amberg N, Hippenmeyer S. Genetic mosaic dissection of candidate genes in mice
using mosaic analysis with double markers. STAR Protocols. 2021;2(4). doi:10.1016/j.xpro.2021.100939
apa: Amberg, N., & Hippenmeyer, S. (2021). Genetic mosaic dissection of candidate
genes in mice using mosaic analysis with double markers. STAR Protocols.
Cell Press. https://doi.org/10.1016/j.xpro.2021.100939
chicago: Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate
Genes in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols.
Cell Press, 2021. https://doi.org/10.1016/j.xpro.2021.100939.
ieee: N. Amberg and S. Hippenmeyer, “Genetic mosaic dissection of candidate genes
in mice using mosaic analysis with double markers,” STAR Protocols, vol.
2, no. 4. Cell Press, 2021.
ista: Amberg N, Hippenmeyer S. 2021. Genetic mosaic dissection of candidate genes
in mice using mosaic analysis with double markers. STAR Protocols. 2(4), 100939.
mla: Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate
Genes in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols,
vol. 2, no. 4, 100939, Cell Press, 2021, doi:10.1016/j.xpro.2021.100939.
short: N. Amberg, S. Hippenmeyer, STAR Protocols 2 (2021).
date_created: 2021-11-21T23:01:28Z
date_published: 2021-11-10T00:00:00Z
date_updated: 2023-11-16T13:08:03Z
day: '10'
ddc:
- '573'
department:
- _id: SiHi
doi: 10.1016/j.xpro.2021.100939
ec_funded: 1
file:
- access_level: open_access
checksum: 9e3f6d06bf583e7a8b6a9e9a60500a28
content_type: application/pdf
creator: cchlebak
date_created: 2021-11-22T08:23:58Z
date_updated: 2021-11-22T08:23:58Z
file_id: '10329'
file_name: 2021_STARProtocols_Amberg.pdf
file_size: 7309464
relation: main_file
success: 1
file_date_updated: 2021-11-22T08:23:58Z
has_accepted_license: '1'
intvolume: ' 2'
issue: '4'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
publication: STAR Protocols
publication_identifier:
eissn:
- 2666-1667
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Genetic mosaic dissection of candidate genes in mice using mosaic analysis
with double markers
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 2
year: '2021'
...
---
_id: '9793'
abstract:
- lang: eng
text: Astrocytes extensively infiltrate the neuropil to regulate critical aspects
of synaptic development and function. This process is regulated by transcellular
interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes
coordinate developmental processes among one another to parse out the synaptic
neuropil and form non-overlapping territories is unknown. Here we identify a molecular
mechanism regulating astrocyte-astrocyte interactions during development to coordinate
astrocyte morphogenesis and gap junction coupling. We show that hepaCAM, a disease-linked,
astrocyte-enriched cell adhesion molecule, regulates astrocyte competition for
territory and morphological complexity in the developing mouse cortex. Furthermore,
conditional deletion of Hepacam from developing astrocytes significantly impairs
gap junction coupling between astrocytes and disrupts the balance between synaptic
excitation and inhibition. Mutations in HEPACAM cause megalencephalic leukoencephalopathy
with subcortical cysts in humans. Therefore, our findings suggest that disruption
of astrocyte self-organization mechanisms could be an underlying cause of neural
pathology.
acknowledgement: This work was supported by the National Institutes of Health (R01
DA047258 and R01 NS102237 to C.E., F32 NS100392 to K.T.B.) and the Holland-Trice
Brain Research Award (to C.E.). K.T.B. was supported by postdoctoral fellowships
from the Foerster-Bernstein Family and The Hartwell Foundation. The Hippenmeyer
lab was supported by the European Research Council (ERC) under the European Union’s
Horizon 2020 research and innovations program (725780 LinPro) to S.H. R.E. was supported
by Ministerio de Ciencia y Tecnología (RTI2018-093493-B-I00). We thank the Duke
Light Microscopy Core Facility, the Duke Transgenic Mouse Facility, Dr. U. Schulte
for assistance with proteomic experiments, and Dr. D. Silver for critical review
of the manuscript. Cartoon elements of figure panels were created using BioRender.com.
article_processing_charge: No
article_type: original
author:
- first_name: Katherine T.
full_name: Baldwin, Katherine T.
last_name: Baldwin
- first_name: Christabel X.
full_name: Tan, Christabel X.
last_name: Tan
- first_name: Samuel T.
full_name: Strader, Samuel T.
last_name: Strader
- first_name: Changyu
full_name: Jiang, Changyu
last_name: Jiang
- first_name: Justin T.
full_name: Savage, Justin T.
last_name: Savage
- first_name: Xabier
full_name: Elorza-Vidal, Xabier
last_name: Elorza-Vidal
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Raúl
full_name: Estévez, Raúl
last_name: Estévez
- first_name: Ru-Rong
full_name: Ji, Ru-Rong
last_name: Ji
- first_name: Cagla
full_name: Eroglu, Cagla
last_name: Eroglu
citation:
ama: Baldwin KT, Tan CX, Strader ST, et al. HepaCAM controls astrocyte self-organization
and coupling. Neuron. 2021;109(15):2427-2442.e10. doi:10.1016/j.neuron.2021.05.025
apa: Baldwin, K. T., Tan, C. X., Strader, S. T., Jiang, C., Savage, J. T., Elorza-Vidal,
X., … Eroglu, C. (2021). HepaCAM controls astrocyte self-organization and coupling.
Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2021.05.025
chicago: Baldwin, Katherine T., Christabel X. Tan, Samuel T. Strader, Changyu Jiang,
Justin T. Savage, Xabier Elorza-Vidal, Ximena Contreras, et al. “HepaCAM Controls
Astrocyte Self-Organization and Coupling.” Neuron. Elsevier, 2021. https://doi.org/10.1016/j.neuron.2021.05.025.
ieee: K. T. Baldwin et al., “HepaCAM controls astrocyte self-organization
and coupling,” Neuron, vol. 109, no. 15. Elsevier, p. 2427–2442.e10, 2021.
ista: Baldwin KT, Tan CX, Strader ST, Jiang C, Savage JT, Elorza-Vidal X, Contreras
X, Rülicke T, Hippenmeyer S, Estévez R, Ji R-R, Eroglu C. 2021. HepaCAM controls
astrocyte self-organization and coupling. Neuron. 109(15), 2427–2442.e10.
mla: Baldwin, Katherine T., et al. “HepaCAM Controls Astrocyte Self-Organization
and Coupling.” Neuron, vol. 109, no. 15, Elsevier, 2021, p. 2427–2442.e10,
doi:10.1016/j.neuron.2021.05.025.
short: K.T. Baldwin, C.X. Tan, S.T. Strader, C. Jiang, J.T. Savage, X. Elorza-Vidal,
X. Contreras, T. Rülicke, S. Hippenmeyer, R. Estévez, R.-R. Ji, C. Eroglu, Neuron
109 (2021) 2427–2442.e10.
date_created: 2021-08-06T09:08:25Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2023-09-27T07:46:09Z
day: '04'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2021.05.025
ec_funded: 1
external_id:
isi:
- '000692851900010'
pmid:
- '34171291'
intvolume: ' 109'
isi: 1
issue: '15'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.neuron.2021.05.025
month: '08'
oa: 1
oa_version: Published Version
page: 2427-2442.e10
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Neuron
publication_identifier:
eissn:
- 1097-4199
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: HepaCAM controls astrocyte self-organization and coupling
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 109
year: '2021'
...
---
_id: '7814'
abstract:
- lang: eng
text: 'Scientific research is to date largely restricted to wealthy laboratories
in developed nations due to the necessity of complex and expensive equipment.
This inequality limits the capacity of science to be used as a diplomatic channel.
Maker movements use open-source technologies including additive manufacturing
(3D printing) and laser cutting, together with low-cost computers for developing
novel products. This movement is setting the groundwork for a revolution, allowing
scientific equipment to be sourced at a fraction of the cost and has the potential
to increase the availability of equipment for scientists around the world. Science
education is increasingly recognized as another channel for science diplomacy.
In this perspective, we introduce the idea that the Maker movement and open-source
technologies have the potential to revolutionize science, technology, engineering
and mathematics (STEM) education worldwide. We present an open-source STEM didactic
tool called SCOPES (Sparking Curiosity through Open-source Platforms in Education
and Science). SCOPES is self-contained, independent of local resources, and cost-effective.
SCOPES can be adapted to communicate complex subjects from genetics to neurobiology,
perform real-world biological experiments and explore digitized scientific samples.
We envision such platforms will enhance science diplomacy by providing a means
for scientists to share their findings with classrooms and for educators to incorporate
didactic concepts into STEM lessons. By providing students the opportunity to
design, perform, and share scientific experiments, students also experience firsthand
the benefits of a multinational scientific community. We provide instructions
on how to build and use SCOPES on our webpage: http://scopeseducation.org.'
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
- _id: EM-Fac
article_number: '48'
article_processing_charge: No
article_type: original
author:
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
citation:
ama: 'Beattie RJ, Hippenmeyer S, Pauler F. SCOPES: Sparking curiosity through Open-Source
platforms in education and science. Frontiers in Education. 2020;5. doi:10.3389/feduc.2020.00048'
apa: 'Beattie, R. J., Hippenmeyer, S., & Pauler, F. (2020). SCOPES: Sparking
curiosity through Open-Source platforms in education and science. Frontiers
in Education. Frontiers Media. https://doi.org/10.3389/feduc.2020.00048'
chicago: 'Beattie, Robert J, Simon Hippenmeyer, and Florian Pauler. “SCOPES: Sparking
Curiosity through Open-Source Platforms in Education and Science.” Frontiers
in Education. Frontiers Media, 2020. https://doi.org/10.3389/feduc.2020.00048.'
ieee: 'R. J. Beattie, S. Hippenmeyer, and F. Pauler, “SCOPES: Sparking curiosity
through Open-Source platforms in education and science,” Frontiers in Education,
vol. 5. Frontiers Media, 2020.'
ista: 'Beattie RJ, Hippenmeyer S, Pauler F. 2020. SCOPES: Sparking curiosity through
Open-Source platforms in education and science. Frontiers in Education. 5, 48.'
mla: 'Beattie, Robert J., et al. “SCOPES: Sparking Curiosity through Open-Source
Platforms in Education and Science.” Frontiers in Education, vol. 5, 48,
Frontiers Media, 2020, doi:10.3389/feduc.2020.00048.'
short: R.J. Beattie, S. Hippenmeyer, F. Pauler, Frontiers in Education 5 (2020).
date_created: 2020-05-11T08:18:48Z
date_published: 2020-05-08T00:00:00Z
date_updated: 2021-01-12T08:15:42Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3389/feduc.2020.00048
ec_funded: 1
file:
- access_level: open_access
checksum: a24ec24e38d843341ae620ec76c53688
content_type: application/pdf
creator: dernst
date_created: 2020-05-11T11:34:08Z
date_updated: 2020-07-14T12:48:03Z
file_id: '7818'
file_name: 2020_FrontiersEduc_Beattie.pdf
file_size: 1402146
relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
intvolume: ' 5'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Frontiers in Education
publication_identifier:
issn:
- 2504-284X
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
status: public
title: 'SCOPES: Sparking curiosity through Open-Source platforms in education and
science'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2020'
...
---
_id: '7815'
abstract:
- lang: eng
text: Beginning from a limited pool of progenitors, the mammalian cerebral cortex
forms highly organized functional neural circuits. However, the underlying cellular
and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs)
and eventual production of neurons and glia in the developing neuroepithelium
remains unclear. Methods to trace NSC division patterns and map the lineage of
clonally related cells have advanced dramatically. However, many contemporary
lineage tracing techniques suffer from the lack of cellular resolution of progeny
cell fate, which is essential for deciphering progenitor cell division patterns.
Presented is a protocol using mosaic analysis with double markers (MADM) to perform
in vivo clonal analysis. MADM concomitantly manipulates individual progenitor
cells and visualizes precise division patterns and lineage progression at unprecedented
single cell resolution. MADM-based interchromosomal recombination events during
the G2-X phase of mitosis, together with temporally inducible CreERT2, provide
exact information on the birth dates of clones and their division patterns. Thus,
MADM lineage tracing provides unprecedented qualitative and quantitative optical
readouts of the proliferation mode of stem cell progenitors at the single cell
level. MADM also allows for examination of the mechanisms and functional requirements
of candidate genes in NSC lineage progression. This method is unique in that comparative
analysis of control and mutant subclones can be performed in the same tissue environment
in vivo. Here, the protocol is described in detail, and experimental paradigms
to employ MADM for clonal analysis and lineage tracing in the developing cerebral
cortex are demonstrated. Importantly, this protocol can be adapted to perform
MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver
is present.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
article_number: e61147
article_processing_charge: No
article_type: original
author:
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Giselle T
full_name: Cheung, Giselle T
id: 471195F6-F248-11E8-B48F-1D18A9856A87
last_name: Cheung
orcid: 0000-0001-8457-2572
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis
in developing cerebral cortex using mosaic analysis with double markers (MADM).
Journal of Visual Experiments. 2020;(159). doi:10.3791/61147
apa: Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen,
A. H., & Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing
cerebral cortex using mosaic analysis with double markers (MADM). Journal of
Visual Experiments. MyJove Corporation. https://doi.org/10.3791/61147
chicago: Beattie, Robert J, Carmen Streicher, Nicole Amberg, Giselle T Cheung, Ximena
Contreras, Andi H Hansen, and Simon Hippenmeyer. “Lineage Tracing and Clonal Analysis
in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).”
Journal of Visual Experiments. MyJove Corporation, 2020. https://doi.org/10.3791/61147.
ieee: R. J. Beattie et al., “Lineage tracing and clonal analysis in developing
cerebral cortex using mosaic analysis with double markers (MADM),” Journal
of Visual Experiments, no. 159. MyJove Corporation, 2020.
ista: Beattie RJ, Streicher C, Amberg N, Cheung GT, Contreras X, Hansen AH, Hippenmeyer
S. 2020. Lineage tracing and clonal analysis in developing cerebral cortex using
mosaic analysis with double markers (MADM). Journal of Visual Experiments. (159),
e61147.
mla: Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing
Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” Journal
of Visual Experiments, no. 159, e61147, MyJove Corporation, 2020, doi:10.3791/61147.
short: R.J. Beattie, C. Streicher, N. Amberg, G.T. Cheung, X. Contreras, A.H. Hansen,
S. Hippenmeyer, Journal of Visual Experiments (2020).
date_created: 2020-05-11T08:31:20Z
date_published: 2020-05-08T00:00:00Z
date_updated: 2024-03-25T23:30:23Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3791/61147
ec_funded: 1
external_id:
isi:
- '000546406600043'
file:
- access_level: open_access
checksum: 3154ea7f90b9fb45e084cd1c2770597d
content_type: application/pdf
creator: rbeattie
date_created: 2020-05-11T08:28:38Z
date_updated: 2020-07-14T12:48:03Z
file_id: '7816'
file_name: jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf
file_size: 1352186
relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
isi: 1
issue: '159'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Journal of Visual Experiments
publication_identifier:
issn:
- 1940-087X
publication_status: published
publisher: MyJove Corporation
quality_controlled: '1'
related_material:
record:
- id: '7902'
relation: part_of_dissertation
status: public
scopus_import: '1'
status: public
title: Lineage tracing and clonal analysis in developing cerebral cortex using mosaic
analysis with double markers (MADM)
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '7902'
abstract:
- lang: eng
text: "Mosaic genetic analysis has been widely used in different model organisms
such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific
fashion. More recently, and less easily conducted, mosaic genetic analysis in
mice has also been enabled with the ambition to shed light on human gene function
and disease. These genetic tools are of particular interest, but not restricted
to, the study of the brain. Notably, the MADM technology offers a genetic approach
in mice to visualize and concomitantly manipulate small subsets of genetically
defined cells at a clonal level and single cell resolution. MADM-based analysis
has already advanced the study of genetic mechanisms regulating brain development
and is expected that further MADM-based analysis of genetic alterations will continue
to reveal important insights on the fundamental principles of development and
disease to potentially assist in the development of new therapies or treatments.\r\nIn
summary, this work completed and characterized the necessary genome-wide genetic
tools to perform MADM-based analysis at single cell level of the vast majority
of mouse genes in virtually any cell type and provided a protocol to perform lineage
tracing using the novel MADM resource. Importantly, this work also explored and
revealed novel aspects of biologically relevant events in an in vivo context,
such as the chromosome-specific bias of chromatid sister segregation pattern,
the generation of cell-type diversity in the cerebral cortex and in the cerebellum
and finally, the relevance of the interplay between the cell-autonomous gene function
and cell-non-autonomous (community) effects in radial glial progenitor lineage
progression.\r\nThis work provides a foundation and opens the door to further
elucidating the molecular mechanisms underlying neuronal diversity and astrocyte
generation."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
citation:
ama: Contreras X. Genetic dissection of neural development in health and disease
at single cell resolution. 2020. doi:10.15479/AT:ISTA:7902
apa: Contreras, X. (2020). Genetic dissection of neural development in health
and disease at single cell resolution. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:7902
chicago: Contreras, Ximena. “Genetic Dissection of Neural Development in Health
and Disease at Single Cell Resolution.” Institute of Science and Technology Austria,
2020. https://doi.org/10.15479/AT:ISTA:7902.
ieee: X. Contreras, “Genetic dissection of neural development in health and disease
at single cell resolution,” Institute of Science and Technology Austria, 2020.
ista: Contreras X. 2020. Genetic dissection of neural development in health and
disease at single cell resolution. Institute of Science and Technology Austria.
mla: Contreras, Ximena. Genetic Dissection of Neural Development in Health and
Disease at Single Cell Resolution. Institute of Science and Technology Austria,
2020, doi:10.15479/AT:ISTA:7902.
short: X. Contreras, Genetic Dissection of Neural Development in Health and Disease
at Single Cell Resolution, Institute of Science and Technology Austria, 2020.
date_created: 2020-05-29T08:27:32Z
date_published: 2020-06-05T00:00:00Z
date_updated: 2023-10-18T08:45:16Z
day: '05'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: SiHi
doi: 10.15479/AT:ISTA:7902
ec_funded: 1
file:
- access_level: closed
checksum: 43c172bf006c95b65992d473c7240d13
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: xcontreras
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project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
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record:
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relation: dissertation_contains
status: public
- id: '28'
relation: dissertation_contains
status: public
- id: '7815'
relation: dissertation_contains
status: public
status: public
supervisor:
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
title: Genetic dissection of neural development in health and disease at single cell
resolution
type: dissertation
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8162'
abstract:
- lang: eng
text: In mammalian genomes, a subset of genes is regulated by genomic imprinting,
resulting in silencing of one parental allele. Imprinting is essential for cerebral
cortex development, but prevalence and functional impact in individual cells is
unclear. Here, we determined allelic expression in cortical cell types and established
a quantitative platform to interrogate imprinting in single cells. We created
cells with uniparental chromosome disomy (UPD) containing two copies of either
the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold
overexpressed or not expressed. By genetic labeling of UPD, we determined cellular
phenotypes and transcriptional responses to deregulated imprinted gene expression
at unprecedented single-cell resolution. We discovered an unexpected degree of
cell-type specificity and a novel function of imprinting in the regulation of
cortical astrocyte survival. More generally, our results suggest functional relevance
of imprinted gene expression in glial astrocyte lineage and thus for generating
cortical cell-type diversity.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit), and A. Seitz and P. Moll (Lexogen GmbH) for technical
support; G. Arque, S. Resch, C. Igler, C. Dotter, C. Yahya, Q. Hudson, and D. Andergassen
for initial experiments and/or assistance; D. Barlow, O. Bell, and all members of
the Hippenmeyer lab for discussion; and N. Barton, B. Vicoso, M. Sixt, and L. Luo
for comments on earlier versions of the manuscript. This research was supported
by the Scientific Service Units (SSU) of IST Austria through resources provided
by the Bioimaging Facilities (BIF), Life Science Facilities (LSF), and Preclinical
Facilities (PCF). A.H.H. is a recipient of a DOC fellowship (24812) of the Austrian
Academy of Sciences. N.A. received support from the FWF Firnberg-Programm (T 1031).
R.B. received support from the FWF Meitner-Programm (M 2416). This work was also
supported by IST Austria institutional funds; a NÖ Forschung und Bildung n[f+b]
life science call grant (C13-002) to S.H.; a program grant from the Human Frontiers
Science Program (RGP0053/2014) to S.H.; the People Programme (Marie Curie Actions)
of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant
agreement 618444 to S.H.; and the European Research Council (ERC) under the European
Union’s Horizon 2020 research and innovation program (grant agreement 725780 LinPro)
to S.H.
article_processing_charge: No
article_type: original
author:
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Thomas
full_name: Penz, Thomas
last_name: Penz
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
orcid: 0000-0001-6091-3088
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting
in cerebral cortex. Neuron. 2020;107(6):1160-1179.e9. doi:10.1016/j.neuron.2020.06.031
apa: Laukoter, S., Pauler, F., Beattie, R. J., Amberg, N., Hansen, A. H., Streicher,
C., … Hippenmeyer, S. (2020). Cell-type specificity of genomic imprinting in cerebral
cortex. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.06.031
chicago: Laukoter, Susanne, Florian Pauler, Robert J Beattie, Nicole Amberg, Andi
H Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, and Simon Hippenmeyer.
“Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” Neuron.
Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.06.031.
ieee: S. Laukoter et al., “Cell-type specificity of genomic imprinting in
cerebral cortex,” Neuron, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020.
ista: Laukoter S, Pauler F, Beattie RJ, Amberg N, Hansen AH, Streicher C, Penz T,
Bock C, Hippenmeyer S. 2020. Cell-type specificity of genomic imprinting in cerebral
cortex. Neuron. 107(6), 1160–1179.e9.
mla: Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral
Cortex.” Neuron, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:10.1016/j.neuron.2020.06.031.
short: S. Laukoter, F. Pauler, R.J. Beattie, N. Amberg, A.H. Hansen, C. Streicher,
T. Penz, C. Bock, S. Hippenmeyer, Neuron 107 (2020) 1160–1179.e9.
date_created: 2020-07-23T16:03:12Z
date_published: 2020-09-23T00:00:00Z
date_updated: 2023-08-22T08:20:11Z
day: '23'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2020.06.031
ec_funded: 1
external_id:
isi:
- '000579698700006'
file:
- access_level: open_access
checksum: 7becdc16a6317304304631087ae7dd7f
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creator: dernst
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intvolume: ' 107'
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language:
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month: '09'
oa: 1
oa_version: Published Version
page: 1160-1179.e9
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
- _id: 25D7962E-B435-11E9-9278-68D0E5697425
grant_number: RGP0053/2014
name: Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal
Level
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Neuron
publication_identifier:
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Website
relation: press_release
url: https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/
scopus_import: '1'
status: public
title: Cell-type specificity of genomic imprinting in cerebral cortex
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 107
year: '2020'
...
---
_id: '8592'
abstract:
- lang: eng
text: Glioblastoma is the most malignant cancer in the brain and currently incurable.
It is urgent to identify effective targets for this lethal disease. Inhibition
of such targets should suppress the growth of cancer cells and, ideally also precancerous
cells for early prevention, but minimally affect their normal counterparts. Using
genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor
cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility
of cells within the development hierarchy of glioma to the knockout of insulin‐like
growth factor I receptor (IGF1R) is determined not only by their oncogenic states,
but also by their cell identities/states. Knockout of IGF1R selectively disrupts
the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable
outcome of IGF1R knockout on cell growth requires the mutant cells to commit to
the OPC identity regardless of its development hierarchical status. At the molecular
level, oncogenic mutations reprogram the cellular network of OPCs and force them
to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally
available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed.
The findings reveal the cellular window of IGF1R targeting and establish IGF1R
as an effective target for the prevention and treatment of glioblastoma.
acknowledgement: The authors thank Drs. J. Eisen, QR. Lu, S. Duan, Z‐H. Li, W. Mo,
and Q. Wu for their critical comments on the manuscript. They also thank Dr. H.
Zong for providing the CKO_NG2‐CreER model. This work is supported by the National
Key Research and Development Program of China, Stem Cell and Translational Research
(2016YFA0101201 to C.L., 2016YFA0100303 to Y.J.W.), the National Natural Science
Foundation of China (81673035 and 81972915 to C.L., 81472722 to Y.J.W.), the Science
Foundation for Distinguished Young Scientists of Zhejiang Province (LR17H160001
to C.L.), Fundamental Research Funds for the Central Universities (2016QNA7023 and
2017QNA7028 to C.L.) and the Thousand Talent Program for Young Outstanding Scientists,
China (to C.L.), IST Austria institutional funds (to S.H.), European Research Council
(ERC) under the European Union's Horizon 2020 research and innovation programme
(725780 LinPro to S.H.). C.L. is a scholar of K. C. Wong Education Foundation.
article_number: '2001724'
article_processing_charge: No
article_type: original
author:
- first_name: Anhao
full_name: Tian, Anhao
last_name: Tian
- first_name: Bo
full_name: Kang, Bo
last_name: Kang
- first_name: Baizhou
full_name: Li, Baizhou
last_name: Li
- first_name: Biying
full_name: Qiu, Biying
last_name: Qiu
- first_name: Wenhong
full_name: Jiang, Wenhong
last_name: Jiang
- first_name: Fangjie
full_name: Shao, Fangjie
last_name: Shao
- first_name: Qingqing
full_name: Gao, Qingqing
last_name: Gao
- first_name: Rui
full_name: Liu, Rui
last_name: Liu
- first_name: Chengwei
full_name: Cai, Chengwei
last_name: Cai
- first_name: Rui
full_name: Jing, Rui
last_name: Jing
- first_name: Wei
full_name: Wang, Wei
last_name: Wang
- first_name: Pengxiang
full_name: Chen, Pengxiang
last_name: Chen
- first_name: Qinghui
full_name: Liang, Qinghui
last_name: Liang
- first_name: Lili
full_name: Bao, Lili
last_name: Bao
- first_name: Jianghong
full_name: Man, Jianghong
last_name: Man
- first_name: Yan
full_name: Wang, Yan
last_name: Wang
- first_name: Yu
full_name: Shi, Yu
last_name: Shi
- first_name: Jin
full_name: Li, Jin
last_name: Li
- first_name: Minmin
full_name: Yang, Minmin
last_name: Yang
- first_name: Lisha
full_name: Wang, Lisha
last_name: Wang
- first_name: Jianmin
full_name: Zhang, Jianmin
last_name: Zhang
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Junming
full_name: Zhu, Junming
last_name: Zhu
- first_name: Xiuwu
full_name: Bian, Xiuwu
last_name: Bian
- first_name: Ying‐Jie
full_name: Wang, Ying‐Jie
last_name: Wang
- first_name: Chong
full_name: Liu, Chong
last_name: Liu
citation:
ama: Tian A, Kang B, Li B, et al. Oncogenic state and cell identity combinatorially
dictate the susceptibility of cells within glioma development hierarchy to IGF1R
targeting. Advanced Science. 2020;7(21). doi:10.1002/advs.202001724
apa: Tian, A., Kang, B., Li, B., Qiu, B., Jiang, W., Shao, F., … Liu, C. (2020).
Oncogenic state and cell identity combinatorially dictate the susceptibility of
cells within glioma development hierarchy to IGF1R targeting. Advanced Science.
Wiley. https://doi.org/10.1002/advs.202001724
chicago: Tian, Anhao, Bo Kang, Baizhou Li, Biying Qiu, Wenhong Jiang, Fangjie Shao,
Qingqing Gao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate
the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.”
Advanced Science. Wiley, 2020. https://doi.org/10.1002/advs.202001724.
ieee: A. Tian et al., “Oncogenic state and cell identity combinatorially
dictate the susceptibility of cells within glioma development hierarchy to IGF1R
targeting,” Advanced Science, vol. 7, no. 21. Wiley, 2020.
ista: Tian A, Kang B, Li B, Qiu B, Jiang W, Shao F, Gao Q, Liu R, Cai C, Jing R,
Wang W, Chen P, Liang Q, Bao L, Man J, Wang Y, Shi Y, Li J, Yang M, Wang L, Zhang
J, Hippenmeyer S, Zhu J, Bian X, Wang Y, Liu C. 2020. Oncogenic state and cell
identity combinatorially dictate the susceptibility of cells within glioma development
hierarchy to IGF1R targeting. Advanced Science. 7(21), 2001724.
mla: Tian, Anhao, et al. “Oncogenic State and Cell Identity Combinatorially Dictate
the Susceptibility of Cells within Glioma Development Hierarchy to IGF1R Targeting.”
Advanced Science, vol. 7, no. 21, 2001724, Wiley, 2020, doi:10.1002/advs.202001724.
short: A. Tian, B. Kang, B. Li, B. Qiu, W. Jiang, F. Shao, Q. Gao, R. Liu, C. Cai,
R. Jing, W. Wang, P. Chen, Q. Liang, L. Bao, J. Man, Y. Wang, Y. Shi, J. Li, M.
Yang, L. Wang, J. Zhang, S. Hippenmeyer, J. Zhu, X. Bian, Y. Wang, C. Liu, Advanced
Science 7 (2020).
date_created: 2020-10-01T09:44:13Z
date_published: 2020-11-04T00:00:00Z
date_updated: 2023-08-22T09:53:01Z
day: '04'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1002/advs.202001724
ec_funded: 1
external_id:
isi:
- '000573860700001'
file:
- access_level: open_access
checksum: 92818c23ecc70e35acfa671f3cfb9909
content_type: application/pdf
creator: dernst
date_created: 2020-12-10T14:07:24Z
date_updated: 2020-12-10T14:07:24Z
file_id: '8938'
file_name: 2020_AdvScience_Tian.pdf
file_size: 7835833
relation: main_file
success: 1
file_date_updated: 2020-12-10T14:07:24Z
has_accepted_license: '1'
intvolume: ' 7'
isi: 1
issue: '21'
keyword:
- General Engineering
- General Physics and Astronomy
- General Materials Science
- Medicine (miscellaneous)
- General Chemical Engineering
- Biochemistry
- Genetics and Molecular Biology (miscellaneous)
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Advanced Science
publication_identifier:
issn:
- 2198-3844
publication_status: published
publisher: Wiley
quality_controlled: '1'
status: public
title: Oncogenic state and cell identity combinatorially dictate the susceptibility
of cells within glioma development hierarchy to IGF1R targeting
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 7
year: '2020'
...
---
_id: '8616'
abstract:
- lang: eng
text: The brain vasculature supplies neurons with glucose and oxygen, but little
is known about how vascular plasticity contributes to brain function. Using longitudinal
in vivo imaging, we reported that a substantial proportion
of blood vessels in the adult brain sporadically occluded and regressed. Their
regression proceeded through sequential stages of blood-flow occlusion, endothelial
cell collapse, relocation or loss of pericytes, and retraction of glial endfeet.
Regressing vessels were found to be widespread in mouse, monkey and human brains.
Both brief occlusions of the middle cerebral artery and lipopolysaccharide-mediated
inflammation induced an increase of vessel regression. Blockage of leukocyte adhesion
to endothelial cells alleviated LPS-induced vessel regression. We further revealed
that blood vessel regression caused a reduction of neuronal activity due to a
dysfunction in mitochondrial metabolism and glutamate production. Our results
elucidate the mechanism of vessel regression and its role in neuronal function
in the adult brain.
acknowledgement: 'The project was initiated in the Jan lab at UCSF. We thank Lily
Jan and Yuh-Nung Jan’s generous support. We thank Liqun Luo’s lab for providing
MADM-7 mice and Rolf A Brekken for VEGF-antibodies. Drs. Yuanquan Song (UPenn),
Zhaozhu Hu (JHU), Ji Hu (ShanghaiTech), Yang Xiang (U. Mass), Hao Wang (Zhejiang
U.) and Ruikang Wang (U. Washington) for critical input, colleagues at Children’s
Research Institute, Departments of Neuroscience, Neurology and Neurotherapeutics,
Pediatrics from UT Southwestern, and colleagues from the Jan lab for discussion.
Dr. Bridget Samuels, Sean Morrison (UT Southwestern), and Nannan Lu (Zhejiang U.)
for critical reading. We acknowledge the assistance of the CIBR Imaging core. We
also thank UT Southwestern Live Cell Imaging Facility, a Shared Resource of the
Harold C. Simmons Cancer Center, supported in part by an NCI Cancer Center Support
Grant, P30 CA142543K. This work is supported by CIBR funds and the American Heart
Association AWRP Summer 2016 Innovative Research Grant (17IRG33410377) to W-P.G.;
National Natural Science Foundation of China (No.81370031) to Z.Z.;National Key
Research and Development Program of China (2016YFE0125400)to F.H.;National Natural
Science Foundations of China (No. 81473202) to Y.L.; National Natural Science Foundation
of China (No.31600839) and Shenzhen Science and Technology Research Program (JCYJ20170818163320865)
to B.P.; National Natural Science Foundation of China (No. 31800864) and Westlake
University start-up funds to J-M. J. NIH R01NS088627 to W.L.J.; NIH: R01 AG020670
and RF1AG054111 to H.Z.; R01 NS088555 to A.M.S., and European Research Council No.725780
to S.H.;W-P.G. was a recipient of Bugher-American Heart Association Dan Adams Thinking
Outside the Box Award.'
article_processing_charge: No
author:
- first_name: Xiaofei
full_name: Gao, Xiaofei
last_name: Gao
- first_name: Jun-Liszt
full_name: Li, Jun-Liszt
last_name: Li
- first_name: Xingjun
full_name: Chen, Xingjun
last_name: Chen
- first_name: Bo
full_name: Ci, Bo
last_name: Ci
- first_name: Fei
full_name: Chen, Fei
last_name: Chen
- first_name: Nannan
full_name: Lu, Nannan
last_name: Lu
- first_name: Bo
full_name: Shen, Bo
last_name: Shen
- first_name: Lijun
full_name: Zheng, Lijun
last_name: Zheng
- first_name: Jie-Min
full_name: Jia, Jie-Min
last_name: Jia
- first_name: Yating
full_name: Yi, Yating
last_name: Yi
- first_name: Shiwen
full_name: Zhang, Shiwen
last_name: Zhang
- first_name: Ying-Chao
full_name: Shi, Ying-Chao
last_name: Shi
- first_name: Kaibin
full_name: Shi, Kaibin
last_name: Shi
- first_name: Nicholas E
full_name: Propson, Nicholas E
last_name: Propson
- first_name: Yubin
full_name: Huang, Yubin
last_name: Huang
- first_name: Katherine
full_name: Poinsatte, Katherine
last_name: Poinsatte
- first_name: Zhaohuan
full_name: Zhang, Zhaohuan
last_name: Zhang
- first_name: Yuanlei
full_name: Yue, Yuanlei
last_name: Yue
- first_name: Dale B
full_name: Bosco, Dale B
last_name: Bosco
- first_name: Ying-mei
full_name: Lu, Ying-mei
last_name: Lu
- first_name: Shi-bing
full_name: Yang, Shi-bing
last_name: Yang
- first_name: Ralf H.
full_name: Adams, Ralf H.
last_name: Adams
- first_name: Volkhard
full_name: Lindner, Volkhard
last_name: Lindner
- first_name: Fen
full_name: Huang, Fen
last_name: Huang
- first_name: Long-Jun
full_name: Wu, Long-Jun
last_name: Wu
- first_name: Hui
full_name: Zheng, Hui
last_name: Zheng
- first_name: Feng
full_name: Han, Feng
last_name: Han
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Ann M.
full_name: Stowe, Ann M.
last_name: Stowe
- first_name: Bo
full_name: Peng, Bo
last_name: Peng
- first_name: Marta
full_name: Margeta, Marta
last_name: Margeta
- first_name: Xiaoqun
full_name: Wang, Xiaoqun
last_name: Wang
- first_name: Qiang
full_name: Liu, Qiang
last_name: Liu
- first_name: Jakob
full_name: Körbelin, Jakob
last_name: Körbelin
- first_name: Martin
full_name: Trepel, Martin
last_name: Trepel
- first_name: Hui
full_name: Lu, Hui
last_name: Lu
- first_name: Bo O.
full_name: Zhou, Bo O.
last_name: Zhou
- first_name: Hu
full_name: Zhao, Hu
last_name: Zhao
- first_name: Wenzhi
full_name: Su, Wenzhi
last_name: Su
- first_name: Robert M.
full_name: Bachoo, Robert M.
last_name: Bachoo
- first_name: Woo-ping
full_name: Ge, Woo-ping
last_name: Ge
citation:
ama: Gao X, Li J-L, Chen X, et al. Reduction of neuronal activity mediated by blood-vessel
regression in the brain. bioRxiv. doi:10.1101/2020.09.15.262782
apa: Gao, X., Li, J.-L., Chen, X., Ci, B., Chen, F., Lu, N., … Ge, W. (n.d.). Reduction
of neuronal activity mediated by blood-vessel regression in the brain. bioRxiv.
Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.09.15.262782
chicago: Gao, Xiaofei, Jun-Liszt Li, Xingjun Chen, Bo Ci, Fei Chen, Nannan Lu, Bo
Shen, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression
in the Brain.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.09.15.262782.
ieee: X. Gao et al., “Reduction of neuronal activity mediated by blood-vessel
regression in the brain,” bioRxiv. Cold Spring Harbor Laboratory.
ista: Gao X, Li J-L, Chen X, Ci B, Chen F, Lu N, Shen B, Zheng L, Jia J-M, Yi Y,
Zhang S, Shi Y-C, Shi K, Propson NE, Huang Y, Poinsatte K, Zhang Z, Yue Y, Bosco
DB, Lu Y, Yang S, Adams RH, Lindner V, Huang F, Wu L-J, Zheng H, Han F, Hippenmeyer
S, Stowe AM, Peng B, Margeta M, Wang X, Liu Q, Körbelin J, Trepel M, Lu H, Zhou
BO, Zhao H, Su W, Bachoo RM, Ge W. Reduction of neuronal activity mediated by
blood-vessel regression in the brain. bioRxiv, 10.1101/2020.09.15.262782.
mla: Gao, Xiaofei, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel
Regression in the Brain.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.09.15.262782.
short: X. Gao, J.-L. Li, X. Chen, B. Ci, F. Chen, N. Lu, B. Shen, L. Zheng, J.-M.
Jia, Y. Yi, S. Zhang, Y.-C. Shi, K. Shi, N.E. Propson, Y. Huang, K. Poinsatte,
Z. Zhang, Y. Yue, D.B. Bosco, Y. Lu, S. Yang, R.H. Adams, V. Lindner, F. Huang,
L.-J. Wu, H. Zheng, F. Han, S. Hippenmeyer, A.M. Stowe, B. Peng, M. Margeta, X.
Wang, Q. Liu, J. Körbelin, M. Trepel, H. Lu, B.O. Zhou, H. Zhao, W. Su, R.M. Bachoo,
W. Ge, BioRxiv (n.d.).
date_created: 2020-10-06T08:58:59Z
date_published: 2020-09-15T00:00:00Z
date_updated: 2021-01-12T08:20:19Z
day: '15'
department:
- _id: SiHi
doi: 10.1101/2020.09.15.262782
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.09.15.262782
month: '09'
oa: 1
oa_version: Preprint
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
status: public
title: Reduction of neuronal activity mediated by blood-vessel regression in the brain
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8949'
abstract:
- lang: eng
text: Development of the nervous system undergoes important transitions,
including one from neurogenesis to gliogenesis which occurs late during embryonic
gestation. Here we report on clonal analysis of gliogenesis in mice using Mosaic
Analysis with Double Markers (MADM) with quantitative and computational methods.
Results reveal that developmental gliogenesis in the cerebral cortex occurs in
a fraction of earlier neurogenic clones, accelerating around E16.5, and giving
rise to both astrocytes and oligodendrocytes. Moreover, MADM-based genetic deletion
of the epidermal growth factor receptor (Egfr) in gliogenic clones revealed that
Egfr is cell autonomously required for gliogenesis in the mouse dorsolateral cortices.
A broad range in the proliferation capacity, symmetry of clones, and competitive
advantage of MADM cells was evident in clones that contained one cellular lineage
with double dosage of Egfr relative to their environment, while their sibling
Egfr-null cells failed to generate glia. Remarkably, the total numbers of glia
in MADM clones balance out regardless of significant alterations in clonal symmetries.
The variability in glial clones shows stochastic patterns that we define mathematically,
which are different from the deterministic patterns in neuronal clones. This study
sets a foundation for studying the biological significance of stochastic and deterministic
clonal principles underlying tissue development, and identifying mechanisms that
differentiate between neurogenesis and gliogenesis.
acknowledgement: This research was funded by grants from the National Institutes of
Health to H.T.G. (R01NS098370 and R01NS089795). C.V.M. was supported by a National
Science Foundation Graduate Research Fellowship (DGE-1746939). R.B. was supported
by the FWF Lise-Meitner program (M 2416), and S.H. was supported by the European
Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
programme (grant agreement No 725780 LinPro).The authors thank members of the Ghashghaei
lab for discussions, technical support, and help with preparation of the manuscript.
article_number: '2662'
article_processing_charge: No
article_type: original
author:
- first_name: Xuying
full_name: Zhang, Xuying
last_name: Zhang
- first_name: Christine V.
full_name: Mennicke, Christine V.
last_name: Mennicke
- first_name: Guanxi
full_name: Xiao, Guanxi
last_name: Xiao
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Mansoor
full_name: Haider, Mansoor
last_name: Haider
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: H. Troy
full_name: Ghashghaei, H. Troy
last_name: Ghashghaei
citation:
ama: Zhang X, Mennicke CV, Xiao G, et al. Clonal analysis of gliogenesis in the
cerebral cortex reveals stochastic expansion of glia and cell autonomous responses
to Egfr dosage. Cells. 2020;9(12). doi:10.3390/cells9122662
apa: Zhang, X., Mennicke, C. V., Xiao, G., Beattie, R. J., Haider, M., Hippenmeyer,
S., & Ghashghaei, H. T. (2020). Clonal analysis of gliogenesis in the cerebral
cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr
dosage. Cells. MDPI. https://doi.org/10.3390/cells9122662
chicago: Zhang, Xuying, Christine V. Mennicke, Guanxi Xiao, Robert J Beattie, Mansoor
Haider, Simon Hippenmeyer, and H. Troy Ghashghaei. “Clonal Analysis of Gliogenesis
in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous
Responses to Egfr Dosage.” Cells. MDPI, 2020. https://doi.org/10.3390/cells9122662.
ieee: X. Zhang et al., “Clonal analysis of gliogenesis in the cerebral cortex
reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage,”
Cells, vol. 9, no. 12. MDPI, 2020.
ista: Zhang X, Mennicke CV, Xiao G, Beattie RJ, Haider M, Hippenmeyer S, Ghashghaei
HT. 2020. Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic
expansion of glia and cell autonomous responses to Egfr dosage. Cells. 9(12),
2662.
mla: Zhang, Xuying, et al. “Clonal Analysis of Gliogenesis in the Cerebral Cortex
Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage.”
Cells, vol. 9, no. 12, 2662, MDPI, 2020, doi:10.3390/cells9122662.
short: X. Zhang, C.V. Mennicke, G. Xiao, R.J. Beattie, M. Haider, S. Hippenmeyer,
H.T. Ghashghaei, Cells 9 (2020).
date_created: 2020-12-14T08:04:03Z
date_published: 2020-12-11T00:00:00Z
date_updated: 2023-08-24T10:57:48Z
day: '11'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3390/cells9122662
ec_funded: 1
external_id:
isi:
- '000601787300001'
file:
- access_level: open_access
checksum: 5095cbdc728c9a510c5761cf60a8861c
content_type: application/pdf
creator: dernst
date_created: 2020-12-14T08:09:43Z
date_updated: 2020-12-14T08:09:43Z
file_id: '8950'
file_name: 2020_Cells_Zhang.pdf
file_size: 3504525
relation: main_file
success: 1
file_date_updated: 2020-12-14T08:09:43Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
issue: '12'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Cells
publication_identifier:
issn:
- 2073-4409
publication_status: published
publisher: MDPI
quality_controlled: '1'
status: public
title: Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion
of glia and cell autonomous responses to Egfr dosage
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 9
year: '2020'
...