Microglial ASD-related genes are involved in oligodendrocyte differentiation

Abstract Autism spectrum disorders (ASD) are associated with mutations of chromodomain-helicase DNA-binding protein 8 (Chd8) and tuberous sclerosis complex 2 (Tsc2). Although these ASD-related genes are detected in glial cells such as microglia, the effect of Chd8 or Tsc2 deficiency on microglial fu...

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Autores principales:	Yuta Takanezawa, Shogo Tanabe, Daiki Kato, Rie Ozeki, Masayo Komoda, Tatsunori Suzuki, Hiroko Baba, Rieko Muramatsu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5a75f1d6512943af8cd72710d5428d1c
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spelling	oai:doaj.org-article:5a75f1d6512943af8cd72710d5428d1c2021-12-02T14:58:46ZMicroglial ASD-related genes are involved in oligodendrocyte differentiation10.1038/s41598-021-97257-92045-2322https://doaj.org/article/5a75f1d6512943af8cd72710d5428d1c2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97257-9https://doaj.org/toc/2045-2322Abstract Autism spectrum disorders (ASD) are associated with mutations of chromodomain-helicase DNA-binding protein 8 (Chd8) and tuberous sclerosis complex 2 (Tsc2). Although these ASD-related genes are detected in glial cells such as microglia, the effect of Chd8 or Tsc2 deficiency on microglial functions and microglia-mediated brain development remains unclear. In this study, we investigated the role of microglial Chd8 and Tsc2 in cytokine expression, phagocytosis activity, and neuro/gliogenesis from neural stem cells (NSCs) in vitro. Chd8 or Tsc2 knockdown in microglia reduced insulin-like growth factor-1(Igf1) expression under lipopolysaccharide (LPS) stimulation. In addition, phagocytosis activity was inhibited by Tsc2 deficiency, microglia-mediated oligodendrocyte development was inhibited, in particular, the differentiation of oligodendrocyte precursor cells to oligodendrocytes was prevented by Chd8 or Tsc2 deficiency. These results suggest that ASD-related gene expression in microglia is involved in oligodendrocyte differentiation, which may contribute to the white matter pathology relating to ASD.Yuta TakanezawaShogo TanabeDaiki KatoRie OzekiMasayo KomodaTatsunori SuzukiHiroko BabaRieko MuramatsuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuta Takanezawa Shogo Tanabe Daiki Kato Rie Ozeki Masayo Komoda Tatsunori Suzuki Hiroko Baba Rieko Muramatsu Microglial ASD-related genes are involved in oligodendrocyte differentiation
description	Abstract Autism spectrum disorders (ASD) are associated with mutations of chromodomain-helicase DNA-binding protein 8 (Chd8) and tuberous sclerosis complex 2 (Tsc2). Although these ASD-related genes are detected in glial cells such as microglia, the effect of Chd8 or Tsc2 deficiency on microglial functions and microglia-mediated brain development remains unclear. In this study, we investigated the role of microglial Chd8 and Tsc2 in cytokine expression, phagocytosis activity, and neuro/gliogenesis from neural stem cells (NSCs) in vitro. Chd8 or Tsc2 knockdown in microglia reduced insulin-like growth factor-1(Igf1) expression under lipopolysaccharide (LPS) stimulation. In addition, phagocytosis activity was inhibited by Tsc2 deficiency, microglia-mediated oligodendrocyte development was inhibited, in particular, the differentiation of oligodendrocyte precursor cells to oligodendrocytes was prevented by Chd8 or Tsc2 deficiency. These results suggest that ASD-related gene expression in microglia is involved in oligodendrocyte differentiation, which may contribute to the white matter pathology relating to ASD.
format	article
author	Yuta Takanezawa Shogo Tanabe Daiki Kato Rie Ozeki Masayo Komoda Tatsunori Suzuki Hiroko Baba Rieko Muramatsu
author_facet	Yuta Takanezawa Shogo Tanabe Daiki Kato Rie Ozeki Masayo Komoda Tatsunori Suzuki Hiroko Baba Rieko Muramatsu
author_sort	Yuta Takanezawa
title	Microglial ASD-related genes are involved in oligodendrocyte differentiation
title_short	Microglial ASD-related genes are involved in oligodendrocyte differentiation
title_full	Microglial ASD-related genes are involved in oligodendrocyte differentiation
title_fullStr	Microglial ASD-related genes are involved in oligodendrocyte differentiation
title_full_unstemmed	Microglial ASD-related genes are involved in oligodendrocyte differentiation
title_sort	microglial asd-related genes are involved in oligodendrocyte differentiation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5a75f1d6512943af8cd72710d5428d1c
work_keys_str_mv	AT yutatakanezawa microglialasdrelatedgenesareinvolvedinoligodendrocytedifferentiation AT shogotanabe microglialasdrelatedgenesareinvolvedinoligodendrocytedifferentiation AT daikikato microglialasdrelatedgenesareinvolvedinoligodendrocytedifferentiation AT rieozeki microglialasdrelatedgenesareinvolvedinoligodendrocytedifferentiation AT masayokomoda microglialasdrelatedgenesareinvolvedinoligodendrocytedifferentiation AT tatsunorisuzuki microglialasdrelatedgenesareinvolvedinoligodendrocytedifferentiation AT hirokobaba microglialasdrelatedgenesareinvolvedinoligodendrocytedifferentiation AT riekomuramatsu microglialasdrelatedgenesareinvolvedinoligodendrocytedifferentiation
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Microglial ASD-related genes are involved in oligodendrocyte differentiation

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