论文库首页  论文库
 
论文编号:
论文题目: BMP restricts stemness of intestinal Lgr5(+) stem cells by directly suppressing their signature genes
英文论文题目: BMP restricts stemness of intestinal Lgr5(+) stem cells by directly suppressing their signature genes
第一作者: Qi, Z; Li, YH; Zhao, B; Xu, C; Liu, Y; Li, HN; Zhang, BJ; Wang, XQ; Yang, X; Xie, W; Li, BJ; Han, JDJ; Chen, YG
英文第一作者: Qi, Z; Li, YH; Zhao, B; Xu, C; Liu, Y; Li, HN; Zhang, BJ; Wang, XQ; Yang, X; Xie, W; Li, BJ; Han, JDJ; Chen, YG
联系作者: Chen, YG (reprint author), Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, State Key Lab Membrane Biol, Beijing 100084, Peoples R China.
英文联系作者: Chen, YG (reprint author), Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, State Key Lab Membrane Biol, Beijing 100084, Peoples R China.
外单位作者单位:
英文外单位作者单位:
发表年度: 2017
卷: 8
期:
页码: 13824
摘要: The intestinal epithelium possesses a remarkable self-renewal ability, which is mediated by actively proliferating Lgr5(+) stem cells. Bone morphogenetic protein (BMP) signalling represents one major counterforce that limits the hyperproliferation of intestinal epithelium, but the exact mechanism remains elusive. Here we demonstrate that epithelial BMP signalling plays an indispensable role in restricting Lgr5(+) stem cell expansion to maintain intestinal homeostasis and prevent premalignant hyperproliferation on damage. Mechanistically, BMP inhibits stemness of Lgr5(+) stem cells through Smad-mediated transcriptional repression of a large number of stem cell signature genes, including Lgr5, and this effect is independent of Wnt/beta-catenin signalling. Smad1/Smad4 recruits histone deacetylase HDAC1 to the promoters to repress transcription, and knockout of Smad4 abolishes the negative effects of BMP on stem cells. Our findings therefore demonstrate that epithelial BMP constrains the Lgr5(+) stem cell self-renewal via Smad-mediated repression of stem cell signature genes to ensure proper homeostatic renewal of intestinal epithelium.
英文摘要: The intestinal epithelium possesses a remarkable self-renewal ability, which is mediated by actively proliferating Lgr5(+) stem cells. Bone morphogenetic protein (BMP) signalling represents one major counterforce that limits the hyperproliferation of intestinal epithelium, but the exact mechanism remains elusive. Here we demonstrate that epithelial BMP signalling plays an indispensable role in restricting Lgr5(+) stem cell expansion to maintain intestinal homeostasis and prevent premalignant hyperproliferation on damage. Mechanistically, BMP inhibits stemness of Lgr5(+) stem cells through Smad-mediated transcriptional repression of a large number of stem cell signature genes, including Lgr5, and this effect is independent of Wnt/beta-catenin signalling. Smad1/Smad4 recruits histone deacetylase HDAC1 to the promoters to repress transcription, and knockout of Smad4 abolishes the negative effects of BMP on stem cells. Our findings therefore demonstrate that epithelial BMP constrains the Lgr5(+) stem cell self-renewal via Smad-mediated repression of stem cell signature genes to ensure proper homeostatic renewal of intestinal epithelium.
刊物名称: NATURE COMMUNICATIONS
英文刊物名称: NATURE COMMUNICATIONS
论文全文:
英文论文全文:
全文链接:
其它备注:
英文其它备注:
学科: Multidisciplinary Sciences
英文学科: Multidisciplinary Sciences
影响因子: 12.124
第一作者所在部门:
英文第一作者所在部门:
论文出处:
英文论文出处:
论文类别: Article
英文论文类别: Article
参与作者:
英文参与作者:
 
2014 中国科学院上海生命科学研究院 版权所有