| Title | NuRD Blocks Reprogramming of Mouse Somatic Cells into Pluripotent Stem Cells |
| Authors | Luo, Min Ling, Te Xie, Wenbing Sun, He Zhou, Yonggang Zhu, Qiaoyun Shen, Meili Zong, Le Lyu, Guoliang Zhao, Yun Ye, Tao Gu, Jun Tao, Wei Lu, Zhigang Grummt, Ingrid |
| Affiliation | Peking Univ, Sch Chem Biol & Biotechnol, Lab Chem Genom, Shenzhen Grad Sch, Shenzhen 518005, Peoples R China. Shenzhen Ctr Dis Control & Prevent, Shenzhen, Peoples R China. Capital Normal Univ, Coll Life Sci, Beijing, Peoples R China. Peking Univ, Key Lab Cell Proliferat & Differentiat, Natl Key Lab Prot Engn & Plant Gene Engn, Minist Educ,Sch Life Sci, Beijing 100871, Peoples R China. Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodeling, Bad Nauheim, Germany. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China. Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Hong Kong, Hong Kong, Peoples R China. DKFZ ZMBH Alliance, German Canc Res Ctr, Div Mol Biol Cell 2, D-69120 Heidelberg, Germany. DKFZ ZMBH Alliance, German Canc Res Ctr, INF 581, D-69120 Heidelberg, Germany. |
| Keywords | Mbd3 NuRD Induced pluripotent stem cells Epigenetic regulation Nanog Reprogramming efficiency SMALL-MOLECULE COMPOUNDS HISTONE DEACETYLASE HUMAN FIBROBLASTS DEFINED FACTORS COMPLEX INDUCTION NANOG COMPONENT EXPRESSION RECRUITMENT |
| Issue Date | 2013 |
| Publisher | stem cells |
| Citation | STEM CELLS.2013,31,(7),1278-1286. |
| Abstract | Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of a defined set of transcription factors requires epigenetic changes in pluripotency genes. Nuclear reprogramming is an inefficient process and the molecular mechanisms that reset the epigenetic state during iPSC generation are largely unknown. Here, we show that downregulation of the nucleosome remodeling and deacetylation (NuRD) complex is required for efficient reprogramming. Overexpression of Mbd3, a subunit of NuRD, inhibits induction of iPSCs by establishing heterochromatic features and silencing embryonic stem cell-specific marker genes, including Oct4 and Nanog. Depletion of Mbd3, on the other hand, improves reprogramming efficiency and facilitates the formation of pluripotent stem cells that are capable of generating viable chimeric mice, even in the absence of c-Myc or Sox2. The results establish Mbd3/NuRD as an important epigenetic regulator that restricts the expression of key pluripotency genes, suggesting that drug-induced downregulation of Mbd3/NuRD may be a powerful means to improve the efficiency and fidelity of reprogramming. STEM Cells2013;31:1278-1286 |
| URI | http://hdl.handle.net/20.500.11897/190359 |
| ISSN | 1066-5099 |
| DOI | 10.1002/stem.1374 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 化学生物学与生物技术学院 生命科学学院 蛋白质与植物基因研究国家重点实验室 细胞增殖分化调控机理研究教育部重点实验室 |
