Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency.
Cell Stem Cell, 2011/4/08;8(4):376-88.
Anokye-Danso F[1], Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE
Affiliations
PMID: 21474102DOI: 10.1016/j.stem.2011.03.001
Impact factor: 25.269
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.
MeSH terms
Animals; Cellular Reprogramming; Humans; Kruppel-Like Factor 4; Mice; MicroRNAs; Pluripotent Stem Cells; Transcription Factors
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