GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27kip1
© 2021. The Author(s)..
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 Sox2CreERT2 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 p27kip1 promoter and could maintain the quiescent state of cochlear SCs by regulating p27kip1 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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2021 |
---|---|
Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
---|---|
Enthalten in: |
Scientific reports - 11(2021), 1 vom: 04. Aug., Seite 15779 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Xu, Jiadong [VerfasserIn] |
---|
Links: |
---|
Themen: |
147604-94-2 |
---|
Anmerkungen: |
Date Completed 23.11.2021 Date Revised 16.07.2022 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.1038/s41598-021-95427-3 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM328936022 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM328936022 | ||
003 | DE-627 | ||
005 | 20231226203407.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2021 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1038/s41598-021-95427-3 |2 doi | |
028 | 5 | 2 | |a pubmed24n1096.xml |
035 | |a (DE-627)NLM328936022 | ||
035 | |a (NLM)34349220 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Xu, Jiadong |e verfasserin |4 aut | |
245 | 1 | 0 | |a GATA3 maintains the quiescent state of cochlear supporting cells by regulating p27kip1 |
264 | 1 | |c 2021 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 23.11.2021 | ||
500 | |a Date Revised 16.07.2022 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2021. The Author(s). | ||
520 | |a 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 Sox2CreERT2 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 p27kip1 promoter and could maintain the quiescent state of cochlear SCs by regulating p27kip1 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 7 | |a Cdkn1b protein, mouse |2 NLM | |
650 | 7 | |a GATA3 Transcription Factor |2 NLM | |
650 | 7 | |a Gata3 protein, mouse |2 NLM | |
650 | 7 | |a Cyclin-Dependent Kinase Inhibitor p27 |2 NLM | |
650 | 7 | |a 147604-94-2 |2 NLM | |
700 | 1 | |a Yu, Dongliang |e verfasserin |4 aut | |
700 | 1 | |a Dong, Xuhui |e verfasserin |4 aut | |
700 | 1 | |a Xie, Xiaoling |e verfasserin |4 aut | |
700 | 1 | |a Xu, Mei |e verfasserin |4 aut | |
700 | 1 | |a Guo, Luming |e verfasserin |4 aut | |
700 | 1 | |a Huang, Liang |e verfasserin |4 aut | |
700 | 1 | |a Tang, Qi |e verfasserin |4 aut | |
700 | 1 | |a Gan, Lin |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Scientific reports |d 2011 |g 11(2021), 1 vom: 04. Aug., Seite 15779 |w (DE-627)NLM215703936 |x 2045-2322 |7 nnns |
773 | 1 | 8 | |g volume:11 |g year:2021 |g number:1 |g day:04 |g month:08 |g pages:15779 |
856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41598-021-95427-3 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 11 |j 2021 |e 1 |b 04 |c 08 |h 15779 |