Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2

Abstract Oligodendrocyte precursor cells (NG2 glia) are uniformly distributed proliferative cells in the mammalian central nervous system and generate myelinating oligodendrocytes throughout life. A subpopulation of OPCs in the neocortex arises from progenitor cells in the embryonic ganglionic emine...

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Autores principales:	Linda L. Boshans, Heun Soh, William M. Wood, Timothy M. Nolan, Ion I. Mandoiu, Yuchio Yanagawa, Anastasios V. Tzingounis, Akiko Nishiyama
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c376f891da9845b0a6362b73b6570587
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spelling	oai:doaj.org-article:c376f891da9845b0a6362b73b65705872021-12-02T12:09:18ZDirect reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx210.1038/s41598-021-82931-92045-2322https://doaj.org/article/c376f891da9845b0a6362b73b65705872021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82931-9https://doaj.org/toc/2045-2322Abstract Oligodendrocyte precursor cells (NG2 glia) are uniformly distributed proliferative cells in the mammalian central nervous system and generate myelinating oligodendrocytes throughout life. A subpopulation of OPCs in the neocortex arises from progenitor cells in the embryonic ganglionic eminences that also produce inhibitory neurons. The neuronal fate of some progenitor cells is sealed before birth as they become committed to the oligodendrocyte lineage, marked by sustained expression of the oligodendrocyte transcription factor Olig2, which represses the interneuron transcription factor Dlx2. Here we show that misexpression of Dlx2 alone in postnatal mouse OPCs caused them to switch their fate to GABAergic neurons within 2 days by downregulating Olig2 and upregulating a network of inhibitory neuron transcripts. After two weeks, some OPC-derived neurons generated trains of action potentials and formed clusters of GABAergic synaptic proteins. Our study revealed that the developmental molecular logic can be applied to promote neuronal reprogramming from OPCs.Linda L. BoshansHeun SohWilliam M. WoodTimothy M. NolanIon I. MandoiuYuchio YanagawaAnastasios V. TzingounisAkiko NishiyamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Linda L. Boshans Heun Soh William M. Wood Timothy M. Nolan Ion I. Mandoiu Yuchio Yanagawa Anastasios V. Tzingounis Akiko Nishiyama Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2
description	Abstract Oligodendrocyte precursor cells (NG2 glia) are uniformly distributed proliferative cells in the mammalian central nervous system and generate myelinating oligodendrocytes throughout life. A subpopulation of OPCs in the neocortex arises from progenitor cells in the embryonic ganglionic eminences that also produce inhibitory neurons. The neuronal fate of some progenitor cells is sealed before birth as they become committed to the oligodendrocyte lineage, marked by sustained expression of the oligodendrocyte transcription factor Olig2, which represses the interneuron transcription factor Dlx2. Here we show that misexpression of Dlx2 alone in postnatal mouse OPCs caused them to switch their fate to GABAergic neurons within 2 days by downregulating Olig2 and upregulating a network of inhibitory neuron transcripts. After two weeks, some OPC-derived neurons generated trains of action potentials and formed clusters of GABAergic synaptic proteins. Our study revealed that the developmental molecular logic can be applied to promote neuronal reprogramming from OPCs.
format	article
author	Linda L. Boshans Heun Soh William M. Wood Timothy M. Nolan Ion I. Mandoiu Yuchio Yanagawa Anastasios V. Tzingounis Akiko Nishiyama
author_facet	Linda L. Boshans Heun Soh William M. Wood Timothy M. Nolan Ion I. Mandoiu Yuchio Yanagawa Anastasios V. Tzingounis Akiko Nishiyama
author_sort	Linda L. Boshans
title	Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2
title_short	Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2
title_full	Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2
title_fullStr	Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2
title_full_unstemmed	Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2
title_sort	direct reprogramming of oligodendrocyte precursor cells into gabaergic inhibitory neurons by a single homeodomain transcription factor dlx2
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c376f891da9845b0a6362b73b6570587
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Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2

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