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Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo

The proneural transcription factor Achaete-scute complex-like 1 (Ascl1) is a major regulator of neural fate decisions, implicated both in neurogenesis and oligodendrogliogenesis. Focusing on its neurogenic activity, Ascl1 has been widely used to reprogram non-neuronal cells into induced neurons. In...

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Autores principales: Galante, Chiara, Marichal, Nicolás, Scarante, Franciele Franco, Ghayad, Litsa Maria, Shi, Youran, Schuurmans, Carol, Berninger, Benedikt, Péron, Sophie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755855/
https://www.ncbi.nlm.nih.gov/pubmed/36532282
http://dx.doi.org/10.3389/fnins.2022.919462
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author Galante, Chiara
Marichal, Nicolás
Scarante, Franciele Franco
Ghayad, Litsa Maria
Shi, Youran
Schuurmans, Carol
Berninger, Benedikt
Péron, Sophie
author_facet Galante, Chiara
Marichal, Nicolás
Scarante, Franciele Franco
Ghayad, Litsa Maria
Shi, Youran
Schuurmans, Carol
Berninger, Benedikt
Péron, Sophie
author_sort Galante, Chiara
collection PubMed
description The proneural transcription factor Achaete-scute complex-like 1 (Ascl1) is a major regulator of neural fate decisions, implicated both in neurogenesis and oligodendrogliogenesis. Focusing on its neurogenic activity, Ascl1 has been widely used to reprogram non-neuronal cells into induced neurons. In vitro, Ascl1 induces efficient reprogramming of proliferative astroglia from the early postnatal cerebral cortex into interneuron-like cells. Here, we examined whether Ascl1 can similarly induce neuronal reprogramming of glia undergoing proliferation in the postnatal mouse cerebral cortex in vivo. Toward this goal, we targeted cortical glia during the peak of proliferative expansion (i.e., postnatal day 5) by injecting a retrovirus encoding for Ascl1 into the mouse cerebral cortex. In contrast to the efficient reprogramming observed in vitro, in vivo Ascl1-transduced glial cells were converted into doublecortin-immunoreactive neurons only with very low efficiency. However, we noted a drastic shift in the relative number of retrovirus-transduced Sox10-positive oligodendrocyte progenitor cells (OPCs) as compared to glial fibrillary acidic protein (GFAP)-positive astrocytes. Genetic fate mapping demonstrated that this increase in OPCs was not due to Ascl1-mediated astrocyte-to-OPC fate conversion. Rather, EdU incorporation experiments revealed that Ascl1 caused a selective increase in proliferative activity of OPCs, but not astrocytes. Our data indicate that rather than inducing neuronal reprogramming of glia in the early postnatal cortex, Ascl1 is a selective enhancer of OPC proliferation.
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spelling pubmed-97558552022-12-17 Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo Galante, Chiara Marichal, Nicolás Scarante, Franciele Franco Ghayad, Litsa Maria Shi, Youran Schuurmans, Carol Berninger, Benedikt Péron, Sophie Front Neurosci Neuroscience The proneural transcription factor Achaete-scute complex-like 1 (Ascl1) is a major regulator of neural fate decisions, implicated both in neurogenesis and oligodendrogliogenesis. Focusing on its neurogenic activity, Ascl1 has been widely used to reprogram non-neuronal cells into induced neurons. In vitro, Ascl1 induces efficient reprogramming of proliferative astroglia from the early postnatal cerebral cortex into interneuron-like cells. Here, we examined whether Ascl1 can similarly induce neuronal reprogramming of glia undergoing proliferation in the postnatal mouse cerebral cortex in vivo. Toward this goal, we targeted cortical glia during the peak of proliferative expansion (i.e., postnatal day 5) by injecting a retrovirus encoding for Ascl1 into the mouse cerebral cortex. In contrast to the efficient reprogramming observed in vitro, in vivo Ascl1-transduced glial cells were converted into doublecortin-immunoreactive neurons only with very low efficiency. However, we noted a drastic shift in the relative number of retrovirus-transduced Sox10-positive oligodendrocyte progenitor cells (OPCs) as compared to glial fibrillary acidic protein (GFAP)-positive astrocytes. Genetic fate mapping demonstrated that this increase in OPCs was not due to Ascl1-mediated astrocyte-to-OPC fate conversion. Rather, EdU incorporation experiments revealed that Ascl1 caused a selective increase in proliferative activity of OPCs, but not astrocytes. Our data indicate that rather than inducing neuronal reprogramming of glia in the early postnatal cortex, Ascl1 is a selective enhancer of OPC proliferation. Frontiers Media S.A. 2022-12-02 /pmc/articles/PMC9755855/ /pubmed/36532282 http://dx.doi.org/10.3389/fnins.2022.919462 Text en Copyright © 2022 Galante, Marichal, Scarante, Ghayad, Shi, Schuurmans, Berninger and Péron. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Galante, Chiara
Marichal, Nicolás
Scarante, Franciele Franco
Ghayad, Litsa Maria
Shi, Youran
Schuurmans, Carol
Berninger, Benedikt
Péron, Sophie
Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo
title Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo
title_full Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo
title_fullStr Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo
title_full_unstemmed Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo
title_short Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo
title_sort enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755855/
https://www.ncbi.nlm.nih.gov/pubmed/36532282
http://dx.doi.org/10.3389/fnins.2022.919462
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