title: Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency.
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.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Anokye-Danso
authors.forename: Chinmay M
authors.initials: CM
authors.lastname: Trivedi
authors.forename: Denise
authors.initials: D
authors.lastname: Juhr
authors.forename: Mudit
authors.initials: M
authors.lastname: Gupta
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cui
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wenli
authors.initials: W
authors.lastname: Yang
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gruber
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Epstein
authors.forename: Edward E
authors.initials: EE
authors.lastname: Morrisey
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000502:physiology
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C558265:MIRN302 microRNA, mouse; C532169:MIRN302A microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors