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Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo

In this study, we have developed highly expandable neural stem cells (NSCs) from HESCs and iPSCs that artificially express the oligodendrocyte (OL) specific transcription factor gene Zfp488. This is enough to restrict them to an exclusive oligodendrocyte progenitor cell (OPC) fate during differentia...

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Autores principales: Biswas, Sangita, Chung, Seung Hyuk, Jiang, Peng, Dehghan, Samaneh, Deng, Wenbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588721/
https://www.ncbi.nlm.nih.gov/pubmed/31227736
http://dx.doi.org/10.1038/s41598-019-45247-3
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author Biswas, Sangita
Chung, Seung Hyuk
Jiang, Peng
Dehghan, Samaneh
Deng, Wenbin
author_facet Biswas, Sangita
Chung, Seung Hyuk
Jiang, Peng
Dehghan, Samaneh
Deng, Wenbin
author_sort Biswas, Sangita
collection PubMed
description In this study, we have developed highly expandable neural stem cells (NSCs) from HESCs and iPSCs that artificially express the oligodendrocyte (OL) specific transcription factor gene Zfp488. This is enough to restrict them to an exclusive oligodendrocyte progenitor cell (OPC) fate during differentiation in vitro and in vivo. During CNS development, Zfp488 is induced during the early stages of OL generation, and then again during terminal differentiation of OLs. Interestingly, the human ortholog Znf488, crucial for OL development in human, has been recently identified to function as a dorsoventral pattering regulator in the ventral spinal cord for the generation of P1, P2/pMN, and P2 neural progenitor domains. Forced expression of Zfp488 gene in human NSCs led to the robust generation of OLs and suppression of neuronal and astrocyte fate in vitro and in vivo. Zfp488 expressing NSC derived oligodendrocytes are functional and can myelinate rat dorsal root ganglion neurons in vitro, and form myelin in Shiverer mice brain in vivo. After transplantation near a site of demyelination, Zfp488 expressing hNSCs migrated to the lesion and differentiated into premyelinating OLs. A certain fraction also homed in the subventricular zone (SVZ). Zfp488-ZsGreen1-hNSC derived OLs formed compact myelin in Shiverer mice brain seen under the electron microscope. Transplanted human neural stem cells (NSC) that have the potential to differentiate into functional oligodendrocytes in response to remyelinating signals can be a powerful therapeutic intervention for disorders where oligodendrocyte (OL) replacement is beneficial.
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spelling pubmed-65887212019-06-28 Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo Biswas, Sangita Chung, Seung Hyuk Jiang, Peng Dehghan, Samaneh Deng, Wenbin Sci Rep Article In this study, we have developed highly expandable neural stem cells (NSCs) from HESCs and iPSCs that artificially express the oligodendrocyte (OL) specific transcription factor gene Zfp488. This is enough to restrict them to an exclusive oligodendrocyte progenitor cell (OPC) fate during differentiation in vitro and in vivo. During CNS development, Zfp488 is induced during the early stages of OL generation, and then again during terminal differentiation of OLs. Interestingly, the human ortholog Znf488, crucial for OL development in human, has been recently identified to function as a dorsoventral pattering regulator in the ventral spinal cord for the generation of P1, P2/pMN, and P2 neural progenitor domains. Forced expression of Zfp488 gene in human NSCs led to the robust generation of OLs and suppression of neuronal and astrocyte fate in vitro and in vivo. Zfp488 expressing NSC derived oligodendrocytes are functional and can myelinate rat dorsal root ganglion neurons in vitro, and form myelin in Shiverer mice brain in vivo. After transplantation near a site of demyelination, Zfp488 expressing hNSCs migrated to the lesion and differentiated into premyelinating OLs. A certain fraction also homed in the subventricular zone (SVZ). Zfp488-ZsGreen1-hNSC derived OLs formed compact myelin in Shiverer mice brain seen under the electron microscope. Transplanted human neural stem cells (NSC) that have the potential to differentiate into functional oligodendrocytes in response to remyelinating signals can be a powerful therapeutic intervention for disorders where oligodendrocyte (OL) replacement is beneficial. Nature Publishing Group UK 2019-06-21 /pmc/articles/PMC6588721/ /pubmed/31227736 http://dx.doi.org/10.1038/s41598-019-45247-3 Text en © The Author(s) 2019 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/.
spellingShingle Article
Biswas, Sangita
Chung, Seung Hyuk
Jiang, Peng
Dehghan, Samaneh
Deng, Wenbin
Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo
title Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo
title_full Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo
title_fullStr Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo
title_full_unstemmed Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo
title_short Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo
title_sort development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588721/
https://www.ncbi.nlm.nih.gov/pubmed/31227736
http://dx.doi.org/10.1038/s41598-019-45247-3
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