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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 5 JUL 2013
Copyright © 2013 AlphaMed Press
Volume 31, Issue 7, pages 1278–1286, July 2013
How to Cite
Luo, M., Ling, T., Xie, W., Sun, H., Zhou, Y., Zhu, Q., Shen, M., Zong, L., Lyu, G., Zhao, Y., Ye, T., Gu, J., Tao, W., Lu, Z. and Grummt, I. (2013), NuRD Blocks Reprogramming of Mouse Somatic Cells into Pluripotent Stem Cells. STEM CELLS, 31: 1278–1286. doi: 10.1002/stem.1374
Author contributions: Z.L., W.T., and I.G.: conception and design, data analysis and interpretation, writing and approval of manuscript; Z.L., M.L., T.L., H.S., and W.X.: collection and assembly of data, data analysis and interpretation; Y.G.Z.: data analysis and interpretation; Q.Z., M.S., L.Z., and G.L.: collection and assembly of data; Y.Z., T.Y., J.G.: other (support of manuscript); M.L., T.L. W.X., and H.S. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
first published online in STEM CELLS EXPRESS March 26, 2013.
- Issue published online: 5 JUL 2013
- Article first published online: 5 JUL 2013
- Accepted manuscript online: 26 MAR 2013 08:22AM EST
- Manuscript Accepted: 15 FEB 2013
- Manuscript Received: 24 SEP 2012
- National Natural Science Foundation of China. Grant Numbers: 30971453, 31171255, 3107116, 30700411, 91219101
- National Basic Research Program of China. Grant Number: 2013CB530700
- Shenzhen Bureau of Science Technology and Information. Grant Number: JC201005260239A
- Chinese Academy of Sciences. Grant Number: XDA01010405
- Induced pluripotent stem cells;
- Epigenetic regulation;
- Reprogramming efficiency
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