Title | 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 |
Author | |
Corresponding Author | Wu, Qiang; Chen, Guokai; Zhang, Wensheng |
Publication Years | 2023-10-01
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DOI | |
Source Title | |
ISSN | 0305-1048
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EISSN | 1362-4962
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Abstract | ["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"] |
URL | [Source Record] |
Indexed By | |
Language | English
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SUSTech Authorship | Others
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WOS Research Area | Biochemistry & Molecular Biology
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WOS Subject | Biochemistry & Molecular Biology
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WOS Accession No | WOS:001087681100001
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Publisher | |
ESI Research Field | BIOLOGY & BIOCHEMISTRY
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Data Source | Web of Science
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Citation statistics | |
Document Type | Journal Article |
Identifier | http://kc.sustech.edu.cn/handle/2SGJ60CL/582850 |
Department | Department of Biology |
Affiliation | 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 |
Recommended Citation 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.
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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.
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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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