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Signal requirement for cortical potential of transplantable human neuroepithelial stem cells
The cerebral cortex develops from dorsal forebrain neuroepithelial progenitor cells. Following the initial expansion of the progenitor cell pool, these cells generate neurons of all the cortical layers and then astrocytes and oligodendrocytes. Yet, the regulatory pathways that control the expansion...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126949/ https://www.ncbi.nlm.nih.gov/pubmed/35606347 http://dx.doi.org/10.1038/s41467-022-29839-8 |
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author | Varga, Balazs V. Faiz, Maryam Pivonkova, Helena Khelifi, Gabriel Yang, Huijuan Gao, Shangbang Linderoth, Emma Zhen, Mei Karadottir, Ragnhildur Thora Hussein, Samer M. Nagy, Andras |
author_facet | Varga, Balazs V. Faiz, Maryam Pivonkova, Helena Khelifi, Gabriel Yang, Huijuan Gao, Shangbang Linderoth, Emma Zhen, Mei Karadottir, Ragnhildur Thora Hussein, Samer M. Nagy, Andras |
author_sort | Varga, Balazs V. |
collection | PubMed |
description | The cerebral cortex develops from dorsal forebrain neuroepithelial progenitor cells. Following the initial expansion of the progenitor cell pool, these cells generate neurons of all the cortical layers and then astrocytes and oligodendrocytes. Yet, the regulatory pathways that control the expansion and maintenance of the progenitor cell pool are currently unknown. Here we define six basic pathway components that regulate proliferation of cortically specified human neuroepithelial stem cells (cNESCs) in vitro without the loss of cerebral cortex developmental potential. We show that activation of FGF and inhibition of BMP and ACTIVIN A signalling are required for long-term cNESC proliferation. We also demonstrate that cNESCs preserve dorsal telencephalon-specific potential when GSK3, AKT and nuclear CATENIN-β1 activity are low. Remarkably, regulation of these six pathway components supports the clonal expansion of cNESCs. Moreover, cNESCs differentiate into lower- and upper-layer cortical neurons in vitro and in vivo. The identification of mechanisms that drive the neuroepithelial stem cell self-renewal and differentiation and preserve this potential in vitro is key to developing regenerative and cell-based therapeutic approaches to treat neurological conditions. |
format | Online Article Text |
id | pubmed-9126949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91269492022-05-25 Signal requirement for cortical potential of transplantable human neuroepithelial stem cells Varga, Balazs V. Faiz, Maryam Pivonkova, Helena Khelifi, Gabriel Yang, Huijuan Gao, Shangbang Linderoth, Emma Zhen, Mei Karadottir, Ragnhildur Thora Hussein, Samer M. Nagy, Andras Nat Commun Article The cerebral cortex develops from dorsal forebrain neuroepithelial progenitor cells. Following the initial expansion of the progenitor cell pool, these cells generate neurons of all the cortical layers and then astrocytes and oligodendrocytes. Yet, the regulatory pathways that control the expansion and maintenance of the progenitor cell pool are currently unknown. Here we define six basic pathway components that regulate proliferation of cortically specified human neuroepithelial stem cells (cNESCs) in vitro without the loss of cerebral cortex developmental potential. We show that activation of FGF and inhibition of BMP and ACTIVIN A signalling are required for long-term cNESC proliferation. We also demonstrate that cNESCs preserve dorsal telencephalon-specific potential when GSK3, AKT and nuclear CATENIN-β1 activity are low. Remarkably, regulation of these six pathway components supports the clonal expansion of cNESCs. Moreover, cNESCs differentiate into lower- and upper-layer cortical neurons in vitro and in vivo. The identification of mechanisms that drive the neuroepithelial stem cell self-renewal and differentiation and preserve this potential in vitro is key to developing regenerative and cell-based therapeutic approaches to treat neurological conditions. Nature Publishing Group UK 2022-05-23 /pmc/articles/PMC9126949/ /pubmed/35606347 http://dx.doi.org/10.1038/s41467-022-29839-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Varga, Balazs V. Faiz, Maryam Pivonkova, Helena Khelifi, Gabriel Yang, Huijuan Gao, Shangbang Linderoth, Emma Zhen, Mei Karadottir, Ragnhildur Thora Hussein, Samer M. Nagy, Andras Signal requirement for cortical potential of transplantable human neuroepithelial stem cells |
title | Signal requirement for cortical potential of transplantable human neuroepithelial stem cells |
title_full | Signal requirement for cortical potential of transplantable human neuroepithelial stem cells |
title_fullStr | Signal requirement for cortical potential of transplantable human neuroepithelial stem cells |
title_full_unstemmed | Signal requirement for cortical potential of transplantable human neuroepithelial stem cells |
title_short | Signal requirement for cortical potential of transplantable human neuroepithelial stem cells |
title_sort | signal requirement for cortical potential of transplantable human neuroepithelial stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126949/ https://www.ncbi.nlm.nih.gov/pubmed/35606347 http://dx.doi.org/10.1038/s41467-022-29839-8 |
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