Lsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells

Abstract Epigenetic mechanisms are known to exert control over gene expression and determine cell fate. Genetic mutations in epigenetic regulators are responsible for several neurologic disorders. Mutations of the chromatin remodeling protein Lsh/HELLS can cause the human Immunodeficiency, Centromer...

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Autores principales:	Yixing Han, Jianke Ren, Eunice Lee, Xiaoping Xu, Weishi Yu, Kathrin Muegge
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a8f0cb628e81496a856554a455852ef3
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spelling	oai:doaj.org-article:a8f0cb628e81496a856554a455852ef32021-12-02T15:05:46ZLsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells10.1038/s41598-017-00804-62045-2322https://doaj.org/article/a8f0cb628e81496a856554a455852ef32017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00804-6https://doaj.org/toc/2045-2322Abstract Epigenetic mechanisms are known to exert control over gene expression and determine cell fate. Genetic mutations in epigenetic regulators are responsible for several neurologic disorders. Mutations of the chromatin remodeling protein Lsh/HELLS can cause the human Immunodeficiency, Centromere instability and Facial anomalies (ICF) syndrome, which is associated with neurologic deficiencies. We report here a critical role for Lsh in murine neural development. Lsh depleted neural stem/progenitor cells (NSPCs) display reduced growth, increases in apoptosis and impaired ability of self-renewal. RNA-seq analysis demonstrates differential gene expression in Lsh−/− NSPCs and suggests multiple aberrant pathways. Concentrating on specific genomic targets, we show that ablation of Lsh alters epigenetic states at specific enhancer regions of the key cell cycle regulator Cdkn1a and the stem cell regulator Bmp4 in NSPCs and alters their expression. These results suggest that Lsh exerts epigenetic regulation at key regulators of neural stem cell fate ensuring adequate NSPCs self-renewal and maintenance during development.Yixing HanJianke RenEunice LeeXiaoping XuWeishi YuKathrin MueggeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yixing Han Jianke Ren Eunice Lee Xiaoping Xu Weishi Yu Kathrin Muegge Lsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells
description	Abstract Epigenetic mechanisms are known to exert control over gene expression and determine cell fate. Genetic mutations in epigenetic regulators are responsible for several neurologic disorders. Mutations of the chromatin remodeling protein Lsh/HELLS can cause the human Immunodeficiency, Centromere instability and Facial anomalies (ICF) syndrome, which is associated with neurologic deficiencies. We report here a critical role for Lsh in murine neural development. Lsh depleted neural stem/progenitor cells (NSPCs) display reduced growth, increases in apoptosis and impaired ability of self-renewal. RNA-seq analysis demonstrates differential gene expression in Lsh−/− NSPCs and suggests multiple aberrant pathways. Concentrating on specific genomic targets, we show that ablation of Lsh alters epigenetic states at specific enhancer regions of the key cell cycle regulator Cdkn1a and the stem cell regulator Bmp4 in NSPCs and alters their expression. These results suggest that Lsh exerts epigenetic regulation at key regulators of neural stem cell fate ensuring adequate NSPCs self-renewal and maintenance during development.
format	article
author	Yixing Han Jianke Ren Eunice Lee Xiaoping Xu Weishi Yu Kathrin Muegge
author_facet	Yixing Han Jianke Ren Eunice Lee Xiaoping Xu Weishi Yu Kathrin Muegge
author_sort	Yixing Han
title	Lsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells
title_short	Lsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells
title_full	Lsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells
title_fullStr	Lsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells
title_full_unstemmed	Lsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells
title_sort	lsh/hells regulates self-renewal/proliferation of neural stem/progenitor cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a8f0cb628e81496a856554a455852ef3
work_keys_str_mv	AT yixinghan lshhellsregulatesselfrenewalproliferationofneuralstemprogenitorcells AT jiankeren lshhellsregulatesselfrenewalproliferationofneuralstemprogenitorcells AT eunicelee lshhellsregulatesselfrenewalproliferationofneuralstemprogenitorcells AT xiaopingxu lshhellsregulatesselfrenewalproliferationofneuralstemprogenitorcells AT weishiyu lshhellsregulatesselfrenewalproliferationofneuralstemprogenitorcells AT kathrinmuegge lshhellsregulatesselfrenewalproliferationofneuralstemprogenitorcells
_version_	1718388723478953984

Lsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells

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