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PTEN negatively regulates the cell lineage progression from NG2(+) glial progenitor to oligodendrocyte via mTOR-independent signaling
Oligodendrocytes (OLs), the myelin-forming CNS glia, are highly vulnerable to cellular stresses, and a severe myelin loss underlies numerous CNS disorders. Expedited OL regeneration may prevent further axonal damage and facilitate functional CNS repair. Although adult OL progenitors (OPCs) are the p...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839742/ https://www.ncbi.nlm.nih.gov/pubmed/29461205 http://dx.doi.org/10.7554/eLife.32021 |
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author | González-Fernández, Estibaliz Jeong, Hey-Kyeong Fukaya, Masahiro Kim, Hyukmin Khawaja, Rabia R Srivastava, Isha N Waisman, Ari Son, Young-Jin Kang, Shin H |
author_facet | González-Fernández, Estibaliz Jeong, Hey-Kyeong Fukaya, Masahiro Kim, Hyukmin Khawaja, Rabia R Srivastava, Isha N Waisman, Ari Son, Young-Jin Kang, Shin H |
author_sort | González-Fernández, Estibaliz |
collection | PubMed |
description | Oligodendrocytes (OLs), the myelin-forming CNS glia, are highly vulnerable to cellular stresses, and a severe myelin loss underlies numerous CNS disorders. Expedited OL regeneration may prevent further axonal damage and facilitate functional CNS repair. Although adult OL progenitors (OPCs) are the primary players for OL regeneration, targetable OPC-specific intracellular signaling mechanisms for facilitated OL regeneration remain elusive. Here, we report that OPC-targeted PTEN inactivation in the mouse, in contrast to OL-specific manipulations, markedly promotes OL differentiation and regeneration in the mature CNS. Unexpectedly, an additional deletion of mTOR did not reverse the enhanced OL development from PTEN-deficient OPCs. Instead, ablation of GSK3β, another downstream signaling molecule that is negatively regulated by PTEN-Akt, enhanced OL development. Our results suggest that PTEN persistently suppresses OL development in an mTOR-independent manner, and at least in part, via controlling GSK3β activity. OPC-targeted PTEN-GSK3β inactivation may benefit facilitated OL regeneration and myelin repair. |
format | Online Article Text |
id | pubmed-5839742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-58397422018-03-09 PTEN negatively regulates the cell lineage progression from NG2(+) glial progenitor to oligodendrocyte via mTOR-independent signaling González-Fernández, Estibaliz Jeong, Hey-Kyeong Fukaya, Masahiro Kim, Hyukmin Khawaja, Rabia R Srivastava, Isha N Waisman, Ari Son, Young-Jin Kang, Shin H eLife Neuroscience Oligodendrocytes (OLs), the myelin-forming CNS glia, are highly vulnerable to cellular stresses, and a severe myelin loss underlies numerous CNS disorders. Expedited OL regeneration may prevent further axonal damage and facilitate functional CNS repair. Although adult OL progenitors (OPCs) are the primary players for OL regeneration, targetable OPC-specific intracellular signaling mechanisms for facilitated OL regeneration remain elusive. Here, we report that OPC-targeted PTEN inactivation in the mouse, in contrast to OL-specific manipulations, markedly promotes OL differentiation and regeneration in the mature CNS. Unexpectedly, an additional deletion of mTOR did not reverse the enhanced OL development from PTEN-deficient OPCs. Instead, ablation of GSK3β, another downstream signaling molecule that is negatively regulated by PTEN-Akt, enhanced OL development. Our results suggest that PTEN persistently suppresses OL development in an mTOR-independent manner, and at least in part, via controlling GSK3β activity. OPC-targeted PTEN-GSK3β inactivation may benefit facilitated OL regeneration and myelin repair. eLife Sciences Publications, Ltd 2018-02-20 /pmc/articles/PMC5839742/ /pubmed/29461205 http://dx.doi.org/10.7554/eLife.32021 Text en © 2018, González-Fernández et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience González-Fernández, Estibaliz Jeong, Hey-Kyeong Fukaya, Masahiro Kim, Hyukmin Khawaja, Rabia R Srivastava, Isha N Waisman, Ari Son, Young-Jin Kang, Shin H PTEN negatively regulates the cell lineage progression from NG2(+) glial progenitor to oligodendrocyte via mTOR-independent signaling |
title | PTEN negatively regulates the cell lineage progression from NG2(+) glial progenitor to oligodendrocyte via mTOR-independent signaling |
title_full | PTEN negatively regulates the cell lineage progression from NG2(+) glial progenitor to oligodendrocyte via mTOR-independent signaling |
title_fullStr | PTEN negatively regulates the cell lineage progression from NG2(+) glial progenitor to oligodendrocyte via mTOR-independent signaling |
title_full_unstemmed | PTEN negatively regulates the cell lineage progression from NG2(+) glial progenitor to oligodendrocyte via mTOR-independent signaling |
title_short | PTEN negatively regulates the cell lineage progression from NG2(+) glial progenitor to oligodendrocyte via mTOR-independent signaling |
title_sort | pten negatively regulates the cell lineage progression from ng2(+) glial progenitor to oligodendrocyte via mtor-independent signaling |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839742/ https://www.ncbi.nlm.nih.gov/pubmed/29461205 http://dx.doi.org/10.7554/eLife.32021 |
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