The core SWI/SNF catalytic subunit Brg1 regulates nephron progenitor cell proliferation and differentiation.
The core SWI/SNF catalytic subunit Brg1 regulates nephron progenitor cell proliferation and differentiation.
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DOI：
10.1016/j.ydbio.2020.05.008
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发表时间：
2020-08-15
影响因子：
2.7
通讯作者：
Rauchman M
中科院分区：
文献类型：
--
作者：
Basta JM;Singh AP;Robbins L;Stout L;Pherson M;Rauchman M
染色质重塑复合体在建立基因表达模式以响应发育信号方面起着关键作用。这些表观遗传调节因子如何决定祖细胞在特定器官发育过程中的命运还不是很清楚。我们发现肾单位前体细胞中SWI/SNF的核心酶蛋白BRG1(SMARCA4)基因缺失会导致严重的肾发育不全。SIX2-Cre、Brg1flx/Flx小鼠肾单位祖细胞因细胞增殖减少而耗尽。这种自我更新的缺陷，加上分化受损，导致BRG1突变肾脏严重的肾单位缺陷。SALL1是肾单位祖细胞扩增和维持所必需的转录因子，与SWI/SNF相关。BRG1和SALL1结合了许多祖细胞基因的启动子，并调节促进其增殖的关键靶点的表达。
Chromatin-remodeling complexes play critical roles in establishing gene expression patterns in response to developmental signals. How these epigenetic regulators determine the fate of progenitor cells during development of specific organs is not well understood. We found that genetic deletion of Brg1 (Smarca4), the core enzymatic protein in SWI/SNF, in nephron progenitor cells leads to severe renal hypoplasia. Nephron progenitor cells were depleted in Six2-Cre, Brg1flx/flx mice due to reduced cell proliferation. This defect in self-renewal, together with impaired differentiation resulted in a profound nephron deficit in Brg1 mutant kidneys. Sall1, a transcription factor that is required for expansion and maintenance of nephron progenitors, associates with SWI/SNF. Brg1 and Sall1 bind promoters of many progenitor cell genes and regulate expression of key targets that promote their proliferation.
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影响因子：
4.6
作者：
Basta, Jeannine M.;Robbins, Lynn;Rauchman, Michael
通讯作者：
Rauchman, Michael
影响因子：
16.6
作者：
Gatchalian J;Malik S;Ho J;Lee DS;Kelso TWR;Shokhirev MN;Dixon JR;Hargreaves DC
通讯作者：
Hargreaves DC
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
2.7
作者：
Hartman, Heather A.;Lai, Hsiao L.;Patterson, Larry T.
通讯作者：
Patterson, Larry T.
影响因子：
4.6
作者：
Blank, Ulrika;Brown, Aaron;Oxburgh, Leif
通讯作者：
Oxburgh, Leif