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Cell Stem Cell. 2011 Apr 8;8(4):376-88. doi: 10.1016/j.stem.2011.03.001.

Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency.

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  • 1Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Erratum in

  • Cell Stem Cell. 2012 Dec 7;11(6):853.

Abstract

Transcription factor-based cellular reprogramming has opened the way to converting somatic cells to a pluripotent state, but has faced limitations resulting from the requirement for transcription factors and the relative inefficiency of the process. We show here that expression of the miR302/367 cluster rapidly and efficiently reprograms mouse and human somatic cells to an iPSC state without a requirement for exogenous transcription factors. This miRNA-based reprogramming approach is two orders of magnitude more efficient than standard Oct4/Sox2/Klf4/Myc-mediated methods. Mouse and human miR302/367 iPSCs display similar characteristics to Oct4/Sox2/Klf4/Myc-iPSCs, including pluripotency marker expression, teratoma formation, and, for mouse cells, chimera contribution and germline contribution. We found that miR367 expression is required for miR302/367-mediated reprogramming and activates Oct4 gene expression, and that suppression of Hdac2 is also required. Thus, our data show that miRNA and Hdac-mediated pathways can cooperate in a powerful way to reprogram somatic cells to pluripotency.

Copyright © 2011 Elsevier Inc. All rights reserved.

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PMID:
21474102
[PubMed - indexed for MEDLINE]
PMCID:
PMC3090650
Free PMC Article

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