---
_id: '11478'
abstract:
- lang: eng
  text: Cerebral organoids differentiated from human-induced pluripotent stem cells
    (hiPSC) provide a unique opportunity to investigate brain development. However,
    organoids usually lack microglia, brain-resident immune cells, which are present
    in the early embryonic brain and participate in neuronal circuit development.
    Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3
    and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol.
    Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented,
    3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When
    we guide the retinal organoid differentiation with low-dosed BMP4, we prevent
    cup development and enhance microglia and 3D-cysts formation. Mass spectrometry
    identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed
    this microglia-preferred environment also within the unguided protocol, providing
    insight into microglial behavior and migration and offer a model to study how
    they enter and distribute within the human brain.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank the scientific service units at ISTA, specifically the lab
  support facility and imaging & optics facility for their support; Nicolas Armel
  for performing the Mass Spectrometry. We thank Alexandra Lang and Tanja Peilnsteiner
  for their help in human brain tissue collection, Rouven Schulz for his insights
  into the functional assays We thank all members of the Siegert group for constant
  feedback on the project and Margaret Maes, Rouven Schulz, and Marco Benevento for
  feedback on the manuscript. This project has received funding from the European
  Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
  program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung
  Niederösterreich (grant No. Sc19-017 to V.H.).
article_number: '104580'
article_processing_charge: Yes
article_type: original
author:
- first_name: Katarina
  full_name: Bartalska, Katarina
  id: 4D883232-F248-11E8-B48F-1D18A9856A87
  last_name: Bartalska
- first_name: Verena
  full_name: Hübschmann, Verena
  id: 32B7C918-F248-11E8-B48F-1D18A9856A87
  last_name: Hübschmann
- first_name: Medina
  full_name: Korkut, Medina
  id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
  last_name: Korkut
  orcid: 0000-0003-4309-2251
- first_name: Ryan J
  full_name: Cubero, Ryan J
  id: 850B2E12-9CD4-11E9-837F-E719E6697425
  last_name: Cubero
  orcid: 0000-0003-0002-1867
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Karl
  full_name: Rössler, Karl
  last_name: Rössler
- first_name: Thomas
  full_name: Czech, Thomas
  last_name: Czech
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
citation:
  ama: Bartalska K, Hübschmann V, Korkut M, et al. A systematic characterization of
    microglia-like cell occurrence during retinal organoid differentiation. <i>iScience</i>.
    2022;25(7). doi:<a href="https://doi.org/10.1016/j.isci.2022.104580">10.1016/j.isci.2022.104580</a>
  apa: Bartalska, K., Hübschmann, V., Korkut, M., Cubero, R. J., Venturino, A., Rössler,
    K., … Siegert, S. (2022). A systematic characterization of microglia-like cell
    occurrence during retinal organoid differentiation. <i>IScience</i>. Elsevier.
    <a href="https://doi.org/10.1016/j.isci.2022.104580">https://doi.org/10.1016/j.isci.2022.104580</a>
  chicago: Bartalska, Katarina, Verena Hübschmann, Medina Korkut, Ryan J Cubero, Alessandro
    Venturino, Karl Rössler, Thomas Czech, and Sandra Siegert. “A Systematic Characterization
    of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” <i>IScience</i>.
    Elsevier, 2022. <a href="https://doi.org/10.1016/j.isci.2022.104580">https://doi.org/10.1016/j.isci.2022.104580</a>.
  ieee: K. Bartalska <i>et al.</i>, “A systematic characterization of microglia-like
    cell occurrence during retinal organoid differentiation,” <i>iScience</i>, vol.
    25, no. 7. Elsevier, 2022.
  ista: Bartalska K, Hübschmann V, Korkut M, Cubero RJ, Venturino A, Rössler K, Czech
    T, Siegert S. 2022. A systematic characterization of microglia-like cell occurrence
    during retinal organoid differentiation. iScience. 25(7), 104580.
  mla: Bartalska, Katarina, et al. “A Systematic Characterization of Microglia-like
    Cell Occurrence during Retinal Organoid Differentiation.” <i>IScience</i>, vol.
    25, no. 7, 104580, Elsevier, 2022, doi:<a href="https://doi.org/10.1016/j.isci.2022.104580">10.1016/j.isci.2022.104580</a>.
  short: K. Bartalska, V. Hübschmann, M. Korkut, R.J. Cubero, A. Venturino, K. Rössler,
    T. Czech, S. Siegert, IScience 25 (2022).
date_created: 2022-07-03T22:01:33Z
date_published: 2022-07-15T00:00:00Z
date_updated: 2023-11-02T12:21:33Z
day: '15'
ddc:
- '610'
department:
- _id: SaSi
doi: 10.1016/j.isci.2022.104580
ec_funded: 1
external_id:
  isi:
  - '000830428500005'
file:
- access_level: open_access
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  creator: cchlebak
  date_created: 2022-07-04T08:19:25Z
  date_updated: 2022-07-04T08:19:25Z
  file_id: '11480'
  file_name: 2022_iScience_Bartalska.pdf
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  relation: main_file
  success: 1
file_date_updated: 2022-07-04T08:19:25Z
has_accepted_license: '1'
intvolume: '        25'
isi: 1
issue: '7'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715571'
  name: Microglia action towards neuronal circuit formation and function in health
    and disease
- _id: B67AFEDC-15C9-11EA-A837-991A96BB2854
  name: IST Austria Open Access Fund
- _id: 9B99D380-BA93-11EA-9121-9846C619BF3A
  grant_number: SC19-017
  name: How human microglia shape developing neurons during health and inflammation
publication: iScience
publication_identifier:
  eissn:
  - 2589-0042
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  record:
  - id: '12117'
    relation: other
    status: public
scopus_import: '1'
status: public
title: A systematic characterization of microglia-like cell occurrence during retinal
  organoid differentiation
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: 25
year: '2022'
...
---
_id: '6412'
abstract:
- lang: eng
  text: Polycomb group (PcG) proteins play critical roles in the epigenetic inheritance
    of cell fate. The Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct
    chromatin modifications to enforce gene silencing, but how transcriptional repression
    is propagated through mitotic cell divisions remains a key unresolved question.
    Using reversible tethering of PcG proteins to ectopic sites in mouse embryonic
    stem cells, here we show that PRC1 can trigger transcriptional repression and
    Polycomb-dependent chromatin modifications. We find that canonical PRC1 (cPRC1),
    but not variant PRC1, maintains gene silencing through cell division upon reversal
    of tethering. Propagation of gene repression is sustained by cis-acting histone
    modifications, PRC2-mediated H3K27me3 and cPRC1-mediated H2AK119ub1, promoting
    a sequence-independent feedback mechanism for PcG protein recruitment. Thus, the
    distinct PRC1 complexes present in vertebrates can differentially regulate epigenetic
    maintenance of gene silencing, potentially enabling dynamic heritable responses
    to complex stimuli. Our findings reveal how PcG repression is potentially inherited
    in vertebrates.
article_number: '1931'
article_processing_charge: No
author:
- first_name: Hagar F.
  full_name: Moussa, Hagar F.
  last_name: Moussa
- first_name: Daniel
  full_name: Bsteh, Daniel
  last_name: Bsteh
- first_name: Ramesh
  full_name: Yelagandula, Ramesh
  last_name: Yelagandula
- first_name: Carina
  full_name: Pribitzer, Carina
  last_name: Pribitzer
- first_name: Karin
  full_name: Stecher, Karin
  last_name: Stecher
- first_name: Katarina
  full_name: Bartalska, Katarina
  id: 4D883232-F248-11E8-B48F-1D18A9856A87
  last_name: Bartalska
- first_name: Luca
  full_name: Michetti, Luca
  last_name: Michetti
- first_name: Jingkui
  full_name: Wang, Jingkui
  last_name: Wang
- first_name: Jorge A.
  full_name: Zepeda-Martinez, Jorge A.
  last_name: Zepeda-Martinez
- first_name: Ulrich
  full_name: Elling, Ulrich
  last_name: Elling
- first_name: Jacob I.
  full_name: Stuckey, Jacob I.
  last_name: Stuckey
- first_name: Lindsey I.
  full_name: James, Lindsey I.
  last_name: James
- first_name: Stephen V.
  full_name: Frye, Stephen V.
  last_name: Frye
- first_name: Oliver
  full_name: Bell, Oliver
  last_name: Bell
citation:
  ama: Moussa HF, Bsteh D, Yelagandula R, et al. Canonical PRC1 controls sequence-independent
    propagation of Polycomb-mediated gene silencing. <i>Nature Communications</i>.
    2019;10(1). doi:<a href="https://doi.org/10.1038/s41467-019-09628-6">10.1038/s41467-019-09628-6</a>
  apa: Moussa, H. F., Bsteh, D., Yelagandula, R., Pribitzer, C., Stecher, K., Bartalska,
    K., … Bell, O. (2019). Canonical PRC1 controls sequence-independent propagation
    of Polycomb-mediated gene silencing. <i>Nature Communications</i>. Springer Nature.
    <a href="https://doi.org/10.1038/s41467-019-09628-6">https://doi.org/10.1038/s41467-019-09628-6</a>
  chicago: Moussa, Hagar F., Daniel Bsteh, Ramesh Yelagandula, Carina Pribitzer, Karin
    Stecher, Katarina Bartalska, Luca Michetti, et al. “Canonical PRC1 Controls Sequence-Independent
    Propagation of Polycomb-Mediated Gene Silencing.” <i>Nature Communications</i>.
    Springer Nature, 2019. <a href="https://doi.org/10.1038/s41467-019-09628-6">https://doi.org/10.1038/s41467-019-09628-6</a>.
  ieee: H. F. Moussa <i>et al.</i>, “Canonical PRC1 controls sequence-independent
    propagation of Polycomb-mediated gene silencing,” <i>Nature Communications</i>,
    vol. 10, no. 1. Springer Nature, 2019.
  ista: Moussa HF, Bsteh D, Yelagandula R, Pribitzer C, Stecher K, Bartalska K, Michetti
    L, Wang J, Zepeda-Martinez JA, Elling U, Stuckey JI, James LI, Frye SV, Bell O.
    2019. Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated
    gene silencing. Nature Communications. 10(1), 1931.
  mla: Moussa, Hagar F., et al. “Canonical PRC1 Controls Sequence-Independent Propagation
    of Polycomb-Mediated Gene Silencing.” <i>Nature Communications</i>, vol. 10, no.
    1, 1931, Springer Nature, 2019, doi:<a href="https://doi.org/10.1038/s41467-019-09628-6">10.1038/s41467-019-09628-6</a>.
  short: H.F. Moussa, D. Bsteh, R. Yelagandula, C. Pribitzer, K. Stecher, K. Bartalska,
    L. Michetti, J. Wang, J.A. Zepeda-Martinez, U. Elling, J.I. Stuckey, L.I. James,
    S.V. Frye, O. Bell, Nature Communications 10 (2019).
date_created: 2019-05-13T07:58:35Z
date_published: 2019-04-29T00:00:00Z
date_updated: 2023-08-25T10:31:56Z
day: '29'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41467-019-09628-6
external_id:
  isi:
  - '000466118700002'
file:
- access_level: open_access
  checksum: 6550a328335396c856db4cbdda7d2994
  content_type: application/pdf
  creator: dernst
  date_created: 2019-05-14T08:45:51Z
  date_updated: 2020-07-14T12:47:29Z
  file_id: '6448'
  file_name: 2019_NatureComm_Moussa.pdf
  file_size: 1223647
  relation: main_file
file_date_updated: 2020-07-14T12:47:29Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
issue: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_identifier:
  eissn:
  - '20411723'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated
  gene silencing
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: 10
year: '2019'
...