BMP restricts stemness of intestinal Lgr5(+) stem cells by directly suppressing their signature genes
文献类型：期刊论文
| 作者 | Qi, Zhen3; Li, Yehua3; Zhao, Bing3; Liu, Yuan3; Li, Haonan3; Zhang, Bingjie3; Xie, Wei3; Chen, Ye-Guang3; Xu, Chi4,5; Han, Jing-Dong Jackie4 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2017 |
| 卷号 | 8期号:-页码:13824 |
| 关键词 | Embryo development single cell expression pattern rule multi-class classification |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/ncomms13824 |
| 文献子类 | Article |
| 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. |
| 学科主题 | Science & Technology - Other Topics |
| WOS关键词 | CONDITIONAL KNOCKOUT MICE ; JUVENILE POLYPOSIS ; SELF-RENEWAL ; COLORECTAL-CANCER ; RNA-SEQ ; CRYPT ; EXPRESSION ; WNT ; EPITHELIUM ; NICHE |
| 语种 | 英语 |
| WOS记录号 | WOS:000391305700001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/618]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Inst Biotechnol, Genet Lab Dev & Dis, State Key Lab Prote, Beijing 100071, Peoples R China; 2.Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Bio X Inst, Shanghai 200240, Peoples R China, 3.Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, State Key Lab Membrane Biol, Beijing 100084, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Partner Inst Computat Biol, Chinese Acad Sci Max Planck,Key Lab Computat Biol, Shanghai 200031, Peoples R China; 5.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China; 6.Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Key Lab Prot Sci,Minist Educ, Beijing 100084, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Qi, Zhen,Li, Yehua,Zhao, Bing,et al. BMP restricts stemness of intestinal Lgr5(+) stem cells by directly suppressing their signature genes[J]. NATURE COMMUNICATIONS,2017,8(-):13824. |
| APA | Qi, Zhen.,Li, Yehua.,Zhao, Bing.,Liu, Yuan.,Li, Haonan.,...&,.(2017).BMP restricts stemness of intestinal Lgr5(+) stem cells by directly suppressing their signature genes.NATURE COMMUNICATIONS,8(-),13824. |
| MLA | Qi, Zhen,et al."BMP restricts stemness of intestinal Lgr5(+) stem cells by directly suppressing their signature genes".NATURE COMMUNICATIONS 8.-(2017):13824. |
入库方式： OAI收割
来源：上海营养与健康研究所
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