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题名

BRD9-mediated control of the TGF-β/Activin/Nodal pathway regulates self-renewal and differentiation of human embryonic stem cells and progression of cancer cells

作者
通讯作者Wu, Qiang; Chen, Guokai; Zhang, Wensheng
发表日期
2023-10-01
DOI
发表期刊
ISSN
0305-1048
EISSN
1362-4962
摘要
["Bromodomain-containing protein 9 (BRD9) is a specific subunit of the non-canonical SWI/SNF (ncBAF) chromatin-remodeling complex, whose function in human embryonic stem cells (hESCs) remains unclear. Here, we demonstrate that impaired BRD9 function reduces the self-renewal capacity of hESCs and alters their differentiation potential. Specifically, BRD9 depletion inhibits meso-endoderm differentiation while promoting neural ectoderm differentiation. Notably, supplementation of NODAL, TGF-beta, Activin A or WNT3A rescues the differentiation defects caused by BRD9 loss. Mechanistically, BRD9 forms a complex with BRD4, SMAD2/3, beta-CATENIN and P300, which regulates the expression of pluripotency genes and the activity of TGF-beta/Nodal/Activin and Wnt signaling pathways. This is achieved by regulating the deposition of H3K27ac on associated genes, thus maintaining and directing hESC differentiation. BRD9-mediated regulation of the TGF-beta/Activin/Nodal pathway is also demonstrated in the development of pancreatic and breast cancer cells. In summary, our study highlights the crucial role of BRD9 in the regulation of hESC self-renewal and differentiation, as well as its participation in the progression of pancreatic and breast cancers.","Graphical Abstract"]
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语种
英语
学校署名
其他
WOS研究方向
Biochemistry & Molecular Biology
WOS类目
Biochemistry & Molecular Biology
WOS记录号
WOS:001087681100001
出版者
ESI学科分类
BIOLOGY & BIOCHEMISTRY
来源库
Web of Science
引用统计
被引频次[WOS]:3
成果类型期刊论文
条目标识符http://sustech.caswiz.com/handle/2SGJ60CL/582850
专题生命科学学院_生物系
生命科学学院
作者单位
1.Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa 999078, Macao, Peoples R China
2.Univ Macau, Fac Hlth Sci, Ctr Reprod Dev & Aging, Taipa 999078, Macao, Peoples R China
3.Soochow Univ, Med Coll, Suzhou 215123, Peoples R China
4.Zhejiang Univ, Zhejiang Univ Univ Edinburgh Inst ZJE, Sch Med, Haining 314400, Peoples R China
5.Binzhou Med Univ, Peninsula Canc Res Ctr, Sch Basic Med Sci, Yantai 264003, Peoples R China
6.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518000, Peoples R China
7.Macau Univ Sci & Technol, Precis Regenerat Med Ctr, Taipa 999078, Macao, Peoples R China
8.Shandong Univ Technol, Sch Life Sci & Med, Zibo 255049, Peoples R China
推荐引用方式
GB/T 7714
Wang, Xuepeng,Song, Chengcheng,Ye, Ying,et al. BRD9-mediated control of the TGF-β/Activin/Nodal pathway regulates self-renewal and differentiation of human embryonic stem cells and progression of cancer cells[J]. NUCLEIC ACIDS RESEARCH,2023.
APA
Wang, Xuepeng.,Song, Chengcheng.,Ye, Ying.,Gu, Yashi.,Li, Xuemei.,...&Zhang, Wensheng.(2023).BRD9-mediated control of the TGF-β/Activin/Nodal pathway regulates self-renewal and differentiation of human embryonic stem cells and progression of cancer cells.NUCLEIC ACIDS RESEARCH.
MLA
Wang, Xuepeng,et al."BRD9-mediated control of the TGF-β/Activin/Nodal pathway regulates self-renewal and differentiation of human embryonic stem cells and progression of cancer cells".NUCLEIC ACIDS RESEARCH (2023).
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