ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord

NG2‐glia are highly proliferative oligodendrocyte precursor cells (OPCs) that are widely distributed throughout the central nervous system (CNS). During development, NG2‐glia predominantly differentiate into oligodendrocytes (OLs) to myelinate axon fibers, but they can also remain as OPCs persisting...

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Autores principales: Kelenis, Demetra P., Hart, Emma, Edwards‐Fligner, Morgan, Johnson, Jane E., Vue, Tou Yia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185776/
https://www.ncbi.nlm.nih.gov/pubmed/29683222
http://dx.doi.org/10.1002/glia.23344
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author Kelenis, Demetra P.
Hart, Emma
Edwards‐Fligner, Morgan
Johnson, Jane E.
Vue, Tou Yia
author_facet Kelenis, Demetra P.
Hart, Emma
Edwards‐Fligner, Morgan
Johnson, Jane E.
Vue, Tou Yia
author_sort Kelenis, Demetra P.
collection PubMed
description NG2‐glia are highly proliferative oligodendrocyte precursor cells (OPCs) that are widely distributed throughout the central nervous system (CNS). During development, NG2‐glia predominantly differentiate into oligodendrocytes (OLs) to myelinate axon fibers, but they can also remain as OPCs persisting into the mature CNS. Interestingly, NG2‐glia in the gray matter (GM) are intrinsically different from those in the white matter (WM) in terms of proliferation, differentiation, gene expression, and electrophysiological properties. Here we investigate the role of the transcriptional regulator, ASCL1, in controlling NG2‐glia distribution and development in the GM and WM. In the spinal cord, ASCL1 levels are higher in WM NG2‐glia than those in the GM. This differential level of ASCL1 in WM and GM NG2‐glia is maintained into adult stages. Long‐term clonal lineage analysis reveals that the progeny of single ASCL1+ oligodendrocyte progenitors (OLPs) and NG2‐glia are primarily restricted to the GM or WM, even though they undergo extensive proliferation to give rise to large clusters of OLs in the postnatal spinal cord. Conditional deletion of Ascl1 specifically in NG2‐glia in the embryonic or adult spinal cord resulted in a significant reduction in the proliferation but not differentiation of these cells. These findings illustrate that ASCL1 is an intrinsic regulator of the proliferative property of NG2‐glia in the CNS.
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spelling pubmed-61857762018-11-15 ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord Kelenis, Demetra P. Hart, Emma Edwards‐Fligner, Morgan Johnson, Jane E. Vue, Tou Yia Glia Research Articles NG2‐glia are highly proliferative oligodendrocyte precursor cells (OPCs) that are widely distributed throughout the central nervous system (CNS). During development, NG2‐glia predominantly differentiate into oligodendrocytes (OLs) to myelinate axon fibers, but they can also remain as OPCs persisting into the mature CNS. Interestingly, NG2‐glia in the gray matter (GM) are intrinsically different from those in the white matter (WM) in terms of proliferation, differentiation, gene expression, and electrophysiological properties. Here we investigate the role of the transcriptional regulator, ASCL1, in controlling NG2‐glia distribution and development in the GM and WM. In the spinal cord, ASCL1 levels are higher in WM NG2‐glia than those in the GM. This differential level of ASCL1 in WM and GM NG2‐glia is maintained into adult stages. Long‐term clonal lineage analysis reveals that the progeny of single ASCL1+ oligodendrocyte progenitors (OLPs) and NG2‐glia are primarily restricted to the GM or WM, even though they undergo extensive proliferation to give rise to large clusters of OLs in the postnatal spinal cord. Conditional deletion of Ascl1 specifically in NG2‐glia in the embryonic or adult spinal cord resulted in a significant reduction in the proliferation but not differentiation of these cells. These findings illustrate that ASCL1 is an intrinsic regulator of the proliferative property of NG2‐glia in the CNS. John Wiley and Sons Inc. 2018-04-23 2018-09 /pmc/articles/PMC6185776/ /pubmed/29683222 http://dx.doi.org/10.1002/glia.23344 Text en © 2018 The Authors GLIA Published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Kelenis, Demetra P.
Hart, Emma
Edwards‐Fligner, Morgan
Johnson, Jane E.
Vue, Tou Yia
ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord
title ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord
title_full ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord
title_fullStr ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord
title_full_unstemmed ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord
title_short ASCL1 regulates proliferation of NG2‐glia in the embryonic and adult spinal cord
title_sort ascl1 regulates proliferation of ng2‐glia in the embryonic and adult spinal cord
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185776/
https://www.ncbi.nlm.nih.gov/pubmed/29683222
http://dx.doi.org/10.1002/glia.23344
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