---
_id: '11067'
abstract:
- lang: eng
  text: Neural progenitor cells (NeuPCs) possess a unique nuclear architecture that
    changes during differentiation. Nucleoporins are linked with cell-type-specific
    gene regulation, coupling physical changes in nuclear structure to transcriptional
    output; but, whether and how they coordinate with key fate-determining transcription
    factors is unclear. Here we show that the nucleoporin Nup153 interacts with Sox2
    in adult NeuPCs, where it is indispensable for their maintenance and controls
    neuronal differentiation. Genome-wide analyses show that Nup153 and Sox2 bind
    and co-regulate hundreds of genes. Binding of Nup153 to gene promoters or transcriptional
    end sites correlates with increased or decreased gene expression, respectively,
    and inhibiting Nup153 expression alters open chromatin configurations at its target
    genes, disrupts genomic localization of Sox2, and promotes differentiation in
    vitro and a gliogenic fate switch in vivo. Together, these findings reveal that
    nuclear structural proteins may exert bimodal transcriptional effects to control
    cell fate.
article_processing_charge: No
article_type: original
author:
- first_name: Tomohisa
  full_name: Toda, Tomohisa
  last_name: Toda
- first_name: Jonathan Y.
  full_name: Hsu, Jonathan Y.
  last_name: Hsu
- first_name: Sara B.
  full_name: Linker, Sara B.
  last_name: Linker
- first_name: Lauren
  full_name: Hu, Lauren
  last_name: Hu
- first_name: Simon T.
  full_name: Schafer, Simon T.
  last_name: Schafer
- first_name: Jerome
  full_name: Mertens, Jerome
  last_name: Mertens
- first_name: Filipe V.
  full_name: Jacinto, Filipe V.
  last_name: Jacinto
- first_name: Martin W
  full_name: HETZER, Martin W
  id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
  last_name: HETZER
  orcid: 0000-0002-2111-992X
- first_name: Fred H.
  full_name: Gage, Fred H.
  last_name: Gage
citation:
  ama: Toda T, Hsu JY, Linker SB, et al. Nup153 interacts with Sox2 to enable bimodal
    gene regulation and maintenance of neural progenitor cells. <i>Cell Stem Cell</i>.
    2017;21(5):618-634.e7. doi:<a href="https://doi.org/10.1016/j.stem.2017.08.012">10.1016/j.stem.2017.08.012</a>
  apa: Toda, T., Hsu, J. Y., Linker, S. B., Hu, L., Schafer, S. T., Mertens, J., …
    Gage, F. H. (2017). Nup153 interacts with Sox2 to enable bimodal gene regulation
    and maintenance of neural progenitor cells. <i>Cell Stem Cell</i>. Elsevier. <a
    href="https://doi.org/10.1016/j.stem.2017.08.012">https://doi.org/10.1016/j.stem.2017.08.012</a>
  chicago: Toda, Tomohisa, Jonathan Y. Hsu, Sara B. Linker, Lauren Hu, Simon T. Schafer,
    Jerome Mertens, Filipe V. Jacinto, Martin Hetzer, and Fred H. Gage. “Nup153 Interacts
    with Sox2 to Enable Bimodal Gene Regulation and Maintenance of Neural Progenitor
    Cells.” <i>Cell Stem Cell</i>. Elsevier, 2017. <a href="https://doi.org/10.1016/j.stem.2017.08.012">https://doi.org/10.1016/j.stem.2017.08.012</a>.
  ieee: T. Toda <i>et al.</i>, “Nup153 interacts with Sox2 to enable bimodal gene
    regulation and maintenance of neural progenitor cells,” <i>Cell Stem Cell</i>,
    vol. 21, no. 5. Elsevier, p. 618–634.e7, 2017.
  ista: Toda T, Hsu JY, Linker SB, Hu L, Schafer ST, Mertens J, Jacinto FV, Hetzer
    M, Gage FH. 2017. Nup153 interacts with Sox2 to enable bimodal gene regulation
    and maintenance of neural progenitor cells. Cell Stem Cell. 21(5), 618–634.e7.
  mla: Toda, Tomohisa, et al. “Nup153 Interacts with Sox2 to Enable Bimodal Gene Regulation
    and Maintenance of Neural Progenitor Cells.” <i>Cell Stem Cell</i>, vol. 21, no.
    5, Elsevier, 2017, p. 618–634.e7, doi:<a href="https://doi.org/10.1016/j.stem.2017.08.012">10.1016/j.stem.2017.08.012</a>.
  short: T. Toda, J.Y. Hsu, S.B. Linker, L. Hu, S.T. Schafer, J. Mertens, F.V. Jacinto,
    M. Hetzer, F.H. Gage, Cell Stem Cell 21 (2017) 618–634.e7.
date_created: 2022-04-07T07:46:12Z
date_published: 2017-11-02T00:00:00Z
date_updated: 2022-07-18T08:33:07Z
day: '02'
doi: 10.1016/j.stem.2017.08.012
extern: '1'
external_id:
  pmid:
  - '28919367'
intvolume: '        21'
issue: '5'
keyword:
- Cell Biology
- Genetics
- Molecular Medicine
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.stem.2017.08.012
month: '11'
oa: 1
oa_version: Published Version
page: 618-634.e7
pmid: 1
publication: Cell Stem Cell
publication_identifier:
  issn:
  - 1934-5909
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nup153 interacts with Sox2 to enable bimodal gene regulation and maintenance
  of neural progenitor cells
type: journal_article
user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd
volume: 21
year: '2017'
...
---
_id: '7141'
article_processing_charge: No
article_type: original
author:
- first_name: Chiara
  full_name: Rolando, Chiara
  last_name: Rolando
- first_name: Andrea
  full_name: Erni, Andrea
  last_name: Erni
- first_name: Alice
  full_name: Grison, Alice
  last_name: Grison
- 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: Anna
  full_name: Engler, Anna
  last_name: Engler
- first_name: Paul J.
  full_name: Gokhale, Paul J.
  last_name: Gokhale
- first_name: Marta
  full_name: Milo, Marta
  last_name: Milo
- first_name: Thomas
  full_name: Wegleiter, Thomas
  last_name: Wegleiter
- first_name: Sebastian
  full_name: Jessberger, Sebastian
  last_name: Jessberger
- first_name: Verdon
  full_name: Taylor, Verdon
  last_name: Taylor
citation:
  ama: Rolando C, Erni A, Grison A, et al. Multipotency of adult hippocampal NSCs
    in vivo is restricted by Drosha/NFIB. <i>Cell Stem Cell</i>. 2016;19(5):653-662.
    doi:<a href="https://doi.org/10.1016/j.stem.2016.07.003">10.1016/j.stem.2016.07.003</a>
  apa: Rolando, C., Erni, A., Grison, A., Beattie, R. J., Engler, A., Gokhale, P.
    J., … Taylor, V. (2016). Multipotency of adult hippocampal NSCs in vivo is restricted
    by Drosha/NFIB. <i>Cell Stem Cell</i>. Elsevier. <a href="https://doi.org/10.1016/j.stem.2016.07.003">https://doi.org/10.1016/j.stem.2016.07.003</a>
  chicago: Rolando, Chiara, Andrea Erni, Alice Grison, Robert J Beattie, Anna Engler,
    Paul J. Gokhale, Marta Milo, Thomas Wegleiter, Sebastian Jessberger, and Verdon
    Taylor. “Multipotency of Adult Hippocampal NSCs in Vivo Is Restricted by Drosha/NFIB.”
    <i>Cell Stem Cell</i>. Elsevier, 2016. <a href="https://doi.org/10.1016/j.stem.2016.07.003">https://doi.org/10.1016/j.stem.2016.07.003</a>.
  ieee: C. Rolando <i>et al.</i>, “Multipotency of adult hippocampal NSCs in vivo
    is restricted by Drosha/NFIB,” <i>Cell Stem Cell</i>, vol. 19, no. 5. Elsevier,
    pp. 653–662, 2016.
  ista: Rolando C, Erni A, Grison A, Beattie RJ, Engler A, Gokhale PJ, Milo M, Wegleiter
    T, Jessberger S, Taylor V. 2016. Multipotency of adult hippocampal NSCs in vivo
    is restricted by Drosha/NFIB. Cell Stem Cell. 19(5), 653–662.
  mla: Rolando, Chiara, et al. “Multipotency of Adult Hippocampal NSCs in Vivo Is
    Restricted by Drosha/NFIB.” <i>Cell Stem Cell</i>, vol. 19, no. 5, Elsevier, 2016,
    pp. 653–62, doi:<a href="https://doi.org/10.1016/j.stem.2016.07.003">10.1016/j.stem.2016.07.003</a>.
  short: C. Rolando, A. Erni, A. Grison, R.J. Beattie, A. Engler, P.J. Gokhale, M.
    Milo, T. Wegleiter, S. Jessberger, V. Taylor, Cell Stem Cell 19 (2016) 653–662.
date_created: 2019-11-28T13:09:09Z
date_published: 2016-08-16T00:00:00Z
date_updated: 2021-01-12T08:12:00Z
day: '16'
doi: 10.1016/j.stem.2016.07.003
extern: '1'
intvolume: '        19'
issue: '5'
language:
- iso: eng
month: '08'
oa_version: None
page: 653-662
publication: Cell Stem Cell
publication_identifier:
  issn:
  - 1934-5909
publication_status: published
publisher: Elsevier
quality_controlled: '1'
status: public
title: Multipotency of adult hippocampal NSCs in vivo is restricted by Drosha/NFIB
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 19
year: '2016'
...
---
_id: '11079'
abstract:
- lang: eng
  text: Aging is a major risk factor for many human diseases, and in vitro generation
    of human neurons is an attractive approach for modeling aging-related brain disorders.
    However, modeling aging in differentiated human neurons has proved challenging.
    We generated neurons from human donors across a broad range of ages, either by
    iPSC-based reprogramming and differentiation or by direct conversion into induced
    neurons (iNs). While iPSCs and derived neurons did not retain aging-associated
    gene signatures, iNs displayed age-specific transcriptional profiles and revealed
    age-associated decreases in the nuclear transport receptor RanBP17. We detected
    an age-dependent loss of nucleocytoplasmic compartmentalization (NCC) in donor
    fibroblasts and corresponding iNs and found that reduced RanBP17 impaired NCC
    in young cells, while iPSC rejuvenation restored NCC in aged cells. These results
    show that iNs retain important aging-related signatures, thus allowing modeling
    of the aging process in vitro, and they identify impaired NCC as an important
    factor in human aging.
article_processing_charge: No
article_type: original
author:
- first_name: Jerome
  full_name: Mertens, Jerome
  last_name: Mertens
- first_name: Apuã C.M.
  full_name: Paquola, Apuã C.M.
  last_name: Paquola
- first_name: Manching
  full_name: Ku, Manching
  last_name: Ku
- first_name: Emily
  full_name: Hatch, Emily
  last_name: Hatch
- first_name: Lena
  full_name: Böhnke, Lena
  last_name: Böhnke
- first_name: Shauheen
  full_name: Ladjevardi, Shauheen
  last_name: Ladjevardi
- first_name: Sean
  full_name: McGrath, Sean
  last_name: McGrath
- first_name: Benjamin
  full_name: Campbell, Benjamin
  last_name: Campbell
- first_name: Hyungjun
  full_name: Lee, Hyungjun
  last_name: Lee
- first_name: Joseph R.
  full_name: Herdy, Joseph R.
  last_name: Herdy
- first_name: J. Tiago
  full_name: Gonçalves, J. Tiago
  last_name: Gonçalves
- first_name: Tomohisa
  full_name: Toda, Tomohisa
  last_name: Toda
- first_name: Yongsung
  full_name: Kim, Yongsung
  last_name: Kim
- first_name: Jürgen
  full_name: Winkler, Jürgen
  last_name: Winkler
- first_name: Jun
  full_name: Yao, Jun
  last_name: Yao
- first_name: Martin W
  full_name: HETZER, Martin W
  id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
  last_name: HETZER
  orcid: 0000-0002-2111-992X
- first_name: Fred H.
  full_name: Gage, Fred H.
  last_name: Gage
citation:
  ama: Mertens J, Paquola ACM, Ku M, et al. Directly reprogrammed human neurons retain
    aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic
    defects. <i>Cell Stem Cell</i>. 2015;17(6):705-718. doi:<a href="https://doi.org/10.1016/j.stem.2015.09.001">10.1016/j.stem.2015.09.001</a>
  apa: Mertens, J., Paquola, A. C. M., Ku, M., Hatch, E., Böhnke, L., Ladjevardi,
    S., … Gage, F. H. (2015). Directly reprogrammed human neurons retain aging-associated
    transcriptomic signatures and reveal age-related nucleocytoplasmic defects. <i>Cell
    Stem Cell</i>. Elsevier. <a href="https://doi.org/10.1016/j.stem.2015.09.001">https://doi.org/10.1016/j.stem.2015.09.001</a>
  chicago: Mertens, Jerome, Apuã C.M. Paquola, Manching Ku, Emily Hatch, Lena Böhnke,
    Shauheen Ladjevardi, Sean McGrath, et al. “Directly Reprogrammed Human Neurons
    Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic
    Defects.” <i>Cell Stem Cell</i>. Elsevier, 2015. <a href="https://doi.org/10.1016/j.stem.2015.09.001">https://doi.org/10.1016/j.stem.2015.09.001</a>.
  ieee: J. Mertens <i>et al.</i>, “Directly reprogrammed human neurons retain aging-associated
    transcriptomic signatures and reveal age-related nucleocytoplasmic defects,” <i>Cell
    Stem Cell</i>, vol. 17, no. 6. Elsevier, pp. 705–718, 2015.
  ista: Mertens J, Paquola ACM, Ku M, Hatch E, Böhnke L, Ladjevardi S, McGrath S,
    Campbell B, Lee H, Herdy JR, Gonçalves JT, Toda T, Kim Y, Winkler J, Yao J, Hetzer
    M, Gage FH. 2015. Directly reprogrammed human neurons retain aging-associated
    transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell
    Stem Cell. 17(6), 705–718.
  mla: Mertens, Jerome, et al. “Directly Reprogrammed Human Neurons Retain Aging-Associated
    Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects.” <i>Cell
    Stem Cell</i>, vol. 17, no. 6, Elsevier, 2015, pp. 705–18, doi:<a href="https://doi.org/10.1016/j.stem.2015.09.001">10.1016/j.stem.2015.09.001</a>.
  short: J. Mertens, A.C.M. Paquola, M. Ku, E. Hatch, L. Böhnke, S. Ladjevardi, S.
    McGrath, B. Campbell, H. Lee, J.R. Herdy, J.T. Gonçalves, T. Toda, Y. Kim, J.
    Winkler, J. Yao, M. Hetzer, F.H. Gage, Cell Stem Cell 17 (2015) 705–718.
date_created: 2022-04-07T07:49:51Z
date_published: 2015-12-03T00:00:00Z
date_updated: 2022-07-18T08:44:21Z
day: '03'
doi: 10.1016/j.stem.2015.09.001
extern: '1'
external_id:
  pmid:
  - '26456686'
intvolume: '        17'
issue: '6'
keyword:
- Cell Biology
- Genetics
- Molecular Medicine
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.stem.2015.09.001
month: '12'
oa: 1
oa_version: Published Version
page: 705-718
pmid: 1
publication: Cell Stem Cell
publication_identifier:
  issn:
  - 1934-5909
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Directly reprogrammed human neurons retain aging-associated transcriptomic
  signatures and reveal age-related nucleocytoplasmic defects
type: journal_article
user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd
volume: 17
year: '2015'
...