Transmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through Ca2+/NFATc3 Signaling

The quiescence, activation, and subsequent neurogenesis of neural stem cells (NSCs) play essential roles in the physiological homeostasis and pathological repair of the central nervous system. Previous studies indicate that transmembrane protein Ttyh1 is required for the stemness of NSCs, whereas th...

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Autores principales:	Yuan Cao, Hai-ning Wu, Xiu-li Cao, Kang-yi Yue, Wen-juan Han, Zi-peng Cao, Yu-fei Zhang, Xiang-yu Gao, Ceng Luo, Xiao-fan Jiang, Hua Han, Min-hua Zheng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	neural stem cell Ttyh1 quiescence neurogenesis stemness Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4d3a91e64ad1442aa65ff3d171f96420
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spelling	oai:doaj.org-article:4d3a91e64ad1442aa65ff3d171f964202021-11-16T05:52:56ZTransmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through Ca2+/NFATc3 Signaling2296-634X10.3389/fcell.2021.779373https://doaj.org/article/4d3a91e64ad1442aa65ff3d171f964202021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.779373/fullhttps://doaj.org/toc/2296-634XThe quiescence, activation, and subsequent neurogenesis of neural stem cells (NSCs) play essential roles in the physiological homeostasis and pathological repair of the central nervous system. Previous studies indicate that transmembrane protein Ttyh1 is required for the stemness of NSCs, whereas the exact functions in vivo and precise mechanisms are still waiting to be elucidated. By constructing Ttyh1-promoter driven reporter mice, we determined the specific expression of Ttyh1 in quiescent NSCs and niche astrocytes. Further evaluations on Ttyh1 knockout mice revealed that Ttyh1 ablation leads to activated neurogenesis and enhanced spatial learning and memory in adult mice (6–8 weeks). Correspondingly, Ttyh1 deficiency results in accelerated exhaustion of NSC pool and impaired neurogenesis in aged mice (12 months). By RNA-sequencing, bioinformatics and molecular biological analysis, we found that Ttyh1 is involved in the regulation of calcium signaling in NSCs, and transcription factor NFATc3 is a critical effector in quiescence versus cell cycle entry regulated by Ttyh1. Our research uncovered new endogenous mechanisms that regulate quiescence versus activation of NSCs, therefore provide novel targets for the intervention to activate quiescent NSCs to participate in injury repair during pathology and aging.Yuan CaoHai-ning WuXiu-li CaoKang-yi YueWen-juan HanZi-peng CaoYu-fei ZhangXiang-yu GaoCeng LuoXiao-fan JiangHua HanMin-hua ZhengFrontiers Media S.A.articleneural stem cellTtyh1quiescenceneurogenesisstemnessBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	neural stem cell Ttyh1 quiescence neurogenesis stemness Biology (General) QH301-705.5
spellingShingle	neural stem cell Ttyh1 quiescence neurogenesis stemness Biology (General) QH301-705.5 Yuan Cao Hai-ning Wu Xiu-li Cao Kang-yi Yue Wen-juan Han Zi-peng Cao Yu-fei Zhang Xiang-yu Gao Ceng Luo Xiao-fan Jiang Hua Han Min-hua Zheng Transmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through Ca2+/NFATc3 Signaling
description	The quiescence, activation, and subsequent neurogenesis of neural stem cells (NSCs) play essential roles in the physiological homeostasis and pathological repair of the central nervous system. Previous studies indicate that transmembrane protein Ttyh1 is required for the stemness of NSCs, whereas the exact functions in vivo and precise mechanisms are still waiting to be elucidated. By constructing Ttyh1-promoter driven reporter mice, we determined the specific expression of Ttyh1 in quiescent NSCs and niche astrocytes. Further evaluations on Ttyh1 knockout mice revealed that Ttyh1 ablation leads to activated neurogenesis and enhanced spatial learning and memory in adult mice (6–8 weeks). Correspondingly, Ttyh1 deficiency results in accelerated exhaustion of NSC pool and impaired neurogenesis in aged mice (12 months). By RNA-sequencing, bioinformatics and molecular biological analysis, we found that Ttyh1 is involved in the regulation of calcium signaling in NSCs, and transcription factor NFATc3 is a critical effector in quiescence versus cell cycle entry regulated by Ttyh1. Our research uncovered new endogenous mechanisms that regulate quiescence versus activation of NSCs, therefore provide novel targets for the intervention to activate quiescent NSCs to participate in injury repair during pathology and aging.
format	article
author	Yuan Cao Hai-ning Wu Xiu-li Cao Kang-yi Yue Wen-juan Han Zi-peng Cao Yu-fei Zhang Xiang-yu Gao Ceng Luo Xiao-fan Jiang Hua Han Min-hua Zheng
author_facet	Yuan Cao Hai-ning Wu Xiu-li Cao Kang-yi Yue Wen-juan Han Zi-peng Cao Yu-fei Zhang Xiang-yu Gao Ceng Luo Xiao-fan Jiang Hua Han Min-hua Zheng
author_sort	Yuan Cao
title	Transmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through Ca2+/NFATc3 Signaling
title_short	Transmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through Ca2+/NFATc3 Signaling
title_full	Transmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through Ca2+/NFATc3 Signaling
title_fullStr	Transmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through Ca2+/NFATc3 Signaling
title_full_unstemmed	Transmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through Ca2+/NFATc3 Signaling
title_sort	transmembrane protein ttyh1 maintains the quiescence of neural stem cells through ca2+/nfatc3 signaling
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4d3a91e64ad1442aa65ff3d171f96420
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Transmembrane Protein Ttyh1 Maintains the Quiescence of Neural Stem Cells Through Ca2+/NFATc3 Signaling

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