气候变化领域集成服务门户(CCPortal): THAP1 modulates oligodendrocyte maturation by regulating ECM degradation in lysosomes

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DOI	10.1073/pnas.2100862118
	THAP1 modulates oligodendrocyte maturation by regulating ECM degradation in lysosomes
	Yellajoshyula D.; Pappas S.S.; Rogers A.E.; Choudhury B.; Reed X.; Ding J.; Cookson M.R.; Shakkottai V.G.; Giger R.J.; Dauer W.T.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:31
英文摘要	Mechanisms controlling myelination during central nervous system (CNS) maturation play a pivotal role in the development and refinement of CNS circuits. The transcription factor THAP1 is essential for timing the inception of myelination during CNS maturation through a cell-autonomous role in the oligodendrocyte lineage. Here, we demonstrate that THAP1 modulates the extracellular matrix (ECM) composition by regulating glycosaminoglycan (GAG) catabolism within oligodendrocyte progenitor cells (OPCs). Thap1-/- OPCs accumulate and secrete excess GAGs, inhibiting their maturation through an autoinhibitory mechanism. THAP1 controls GAG metabolism by binding to and regulating the GusB gene encoding β-glucuronidase, a GAG-catabolic lysosomal enzyme. Applying GAGdegrading enzymes or overexpressing β-glucuronidase rescues Thap1-/- OL maturation deficits in vitro and in vivo. Our studies establish lysosomal GAG catabolism within OPCs as a critical mechanism regulating oligodendrocyte development. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CNS myelination; Extracellular matrix; Neurodevelopmental disease
语种	英语
scopus关键词	beta glucuronidase; chondroitin 4 sulfate; chondroitin sulfate; hyaluronic acid; transcription factor; transcription factor THAP1; unclassified drug; DNA binding protein; THAP1 protein, mouse; animal cell; animal experiment; Article; catabolism; cell differentiation; cell maturation; central nervous system; controlled study; cortical thickness (brain); differential gene expression; enzymatic degradation; enzyme activity; extracellular matrix degradation; gene ontology; gene overexpression; glycosaminoglycan metabolism; immunohistochemistry; in vitro study; in vivo study; liquid chromatography-mass spectrometry; loss of function mutation; lysosome; mouse; mRNA expression level; myelination; nonhuman; oligodendrocyte precursor cell; oligodendroglia; paracrine signaling; pathway enrichment analysis; regulatory mechanism; transcriptomics; animal; extracellular matrix; gene expression regulation; genetics; knockout mouse; metabolism; Animals; DNA-Binding Proteins; Extracellular Matrix; Gene Expression Regulation; Lysosomes; Mice; Mice, Knockout
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251102
作者单位	Department of Neurology, University of Michigan, Ann Arbor, MI 48109, United States; Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Department of Cellular and Molecular Medicine, University of California San Diego, San diego, CA 92093, United States; Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute of Aging, NIH, Bethesda, MD 20892, United States; Department of Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, United States; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
推荐引用方式 GB/T 7714	Yellajoshyula D.,Pappas S.S.,Rogers A.E.,et al. THAP1 modulates oligodendrocyte maturation by regulating ECM degradation in lysosomes[J],2021,118(31).
APA	Yellajoshyula D..,Pappas S.S..,Rogers A.E..,Choudhury B..,Reed X..,...&Dauer W.T..(2021).THAP1 modulates oligodendrocyte maturation by regulating ECM degradation in lysosomes.Proceedings of the National Academy of Sciences of the United States of America,118(31).
MLA	Yellajoshyula D.,et al."THAP1 modulates oligodendrocyte maturation by regulating ECM degradation in lysosomes".Proceedings of the National Academy of Sciences of the United States of America 118.31(2021).