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

Frederick Anokye-Danso, Chinmay M. Trivedi, Denise Juhr, Mudit Gupta, Zheng Cui, Ying Tian, Yuzhen Zhang, Wenli Yang, Peter J. Gruber, Jonathan A. Epstein, Edward E. Morrisey

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)376-388
Number of pages13
JournalCell Stem Cell
Volume8
Issue number4
DOIs
StatePublished - Apr 8 2011
Externally publishedYes

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MicroRNAs
Transcription Factors
Teratoma
Gene Expression

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. / Anokye-Danso, Frederick; Trivedi, Chinmay M.; Juhr, Denise; Gupta, Mudit; Cui, Zheng; Tian, Ying; Zhang, Yuzhen; Yang, Wenli; Gruber, Peter J.; Epstein, Jonathan A.; Morrisey, Edward E.

In: Cell Stem Cell, Vol. 8, No. 4, 08.04.2011, p. 376-388.

Research output: Contribution to journalArticle

Anokye-Danso, F, Trivedi, CM, Juhr, D, Gupta, M, Cui, Z, Tian, Y, Zhang, Y, Yang, W, Gruber, PJ, Epstein, JA & Morrisey, EE 2011, 'Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency', Cell Stem Cell, vol. 8, no. 4, pp. 376-388. https://doi.org/10.1016/j.stem.2011.03.001
Anokye-Danso, Frederick ; Trivedi, Chinmay M. ; Juhr, Denise ; Gupta, Mudit ; Cui, Zheng ; Tian, Ying ; Zhang, Yuzhen ; Yang, Wenli ; Gruber, Peter J. ; Epstein, Jonathan A. ; Morrisey, Edward E. / Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. In: Cell Stem Cell. 2011 ; Vol. 8, No. 4. pp. 376-388.
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