GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27kip1

Abstract Haplo-insufficiency of the GATA3 gene causes hypoparathyroidism, sensorineural hearing loss, and renal disease (HDR) syndrome. Previous studies have shown that Gata3 is required for the development of the prosensory domain and spiral ganglion neurons (SGNs) of the mouse cochlea during embry...

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Autores principales:	Jiadong Xu, Dongliang Yu, Xuhui Dong, Xiaoling Xie, Mei Xu, Luming Guo, Liang Huang, Qi Tang, Lin Gan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/23c3e3f6c1b441e0bcc5c88826456c7e
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spelling	oai:doaj.org-article:23c3e3f6c1b441e0bcc5c88826456c7e2021-12-02T14:53:49ZGATA3 maintains the quiescent state of cochlear supporting cells by regulating p27kip110.1038/s41598-021-95427-32045-2322https://doaj.org/article/23c3e3f6c1b441e0bcc5c88826456c7e2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95427-3https://doaj.org/toc/2045-2322Abstract Haplo-insufficiency of the GATA3 gene causes hypoparathyroidism, sensorineural hearing loss, and renal disease (HDR) syndrome. Previous studies have shown that Gata3 is required for the development of the prosensory domain and spiral ganglion neurons (SGNs) of the mouse cochlea during embryogenesis. However, its role in supporting cells (SCs) after cell fate specification is largely unknown. In this study, we used tamoxifen-inducible Sox2 CreERT2 mice to delete Gata3 in SCs of the neonatal mouse cochlea and showed that loss of Gata3 resulted in the proliferation of SCs, including the inner pillar cells (IPCs), inner border cells (IBCs), and lateral greater epithelium ridge (GER). In addition, loss of Gata3 resulted in the down-regulation of p27kip1, a cell cycle inhibitor, in the SCs of Gata3-CKO neonatal cochleae. Chromatin immunoprecipitation analysis revealed that GATA3 directly binds to p27 kip1 promoter and could maintain the quiescent state of cochlear SCs by regulating p27 kip1 expression. Furthermore, RNA-seq analysis revealed that loss of Gata3 function resulted in the change in the expression of genes essential for the development and function of cochlear SCs, including Tectb, Cyp26b1, Slitrk6, Ano1, and Aqp4.Jiadong XuDongliang YuXuhui DongXiaoling XieMei XuLuming GuoLiang HuangQi TangLin GanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiadong Xu Dongliang Yu Xuhui Dong Xiaoling Xie Mei Xu Luming Guo Liang Huang Qi Tang Lin Gan GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27kip1
description	Abstract Haplo-insufficiency of the GATA3 gene causes hypoparathyroidism, sensorineural hearing loss, and renal disease (HDR) syndrome. Previous studies have shown that Gata3 is required for the development of the prosensory domain and spiral ganglion neurons (SGNs) of the mouse cochlea during embryogenesis. However, its role in supporting cells (SCs) after cell fate specification is largely unknown. In this study, we used tamoxifen-inducible Sox2 CreERT2 mice to delete Gata3 in SCs of the neonatal mouse cochlea and showed that loss of Gata3 resulted in the proliferation of SCs, including the inner pillar cells (IPCs), inner border cells (IBCs), and lateral greater epithelium ridge (GER). In addition, loss of Gata3 resulted in the down-regulation of p27kip1, a cell cycle inhibitor, in the SCs of Gata3-CKO neonatal cochleae. Chromatin immunoprecipitation analysis revealed that GATA3 directly binds to p27 kip1 promoter and could maintain the quiescent state of cochlear SCs by regulating p27 kip1 expression. Furthermore, RNA-seq analysis revealed that loss of Gata3 function resulted in the change in the expression of genes essential for the development and function of cochlear SCs, including Tectb, Cyp26b1, Slitrk6, Ano1, and Aqp4.
format	article
author	Jiadong Xu Dongliang Yu Xuhui Dong Xiaoling Xie Mei Xu Luming Guo Liang Huang Qi Tang Lin Gan
author_facet	Jiadong Xu Dongliang Yu Xuhui Dong Xiaoling Xie Mei Xu Luming Guo Liang Huang Qi Tang Lin Gan
author_sort	Jiadong Xu
title	GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27kip1
title_short	GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27kip1
title_full	GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27kip1
title_fullStr	GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27kip1
title_full_unstemmed	GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27kip1
title_sort	gata3 maintains the quiescent state of cochlear supporting cells by regulating p27kip1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/23c3e3f6c1b441e0bcc5c88826456c7e
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GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27kip1

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