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

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.

Pubmed ID: 21474102

Authors

  • Anokye-Danso F
  • Trivedi CM
  • Juhr D
  • Gupta M
  • Cui Z
  • Tian Y
  • Zhang Y
  • Yang W
  • Gruber PJ
  • Epstein JA
  • Morrisey EE

Journal

Cell stem cell

Publication Data

April 8, 2011

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL064632
  • Agency: NHLBI NIH HHS, Id: HL087825
  • Agency: NHLBI NIH HHS, Id: HL098366
  • Agency: NHLBI NIH HHS, Id: HL100405
  • Agency: NHLBI NIH HHS, Id: K99 HL098366
  • Agency: NHLBI NIH HHS, Id: K99 HL098366-01
  • Agency: NHLBI NIH HHS, Id: K99 HL098366-02
  • Agency: NHLBI NIH HHS, Id: R00 HL098366
  • Agency: NHLBI NIH HHS, Id: R01 HL064632
  • Agency: NHLBI NIH HHS, Id: R01 HL064632-12
  • Agency: NHLBI NIH HHS, Id: R01 HL087825
  • Agency: NHLBI NIH HHS, Id: R01 HL087825-01A1
  • Agency: NHLBI NIH HHS, Id: U01 HL100405
  • Agency: NHLBI NIH HHS, Id: U01 HL100405-01

Mesh Terms

  • Animals
  • Cellular Reprogramming
  • Humans
  • Mice
  • MicroRNAs
  • Pluripotent Stem Cells
  • Transcription Factors