Multiple Targets of MiR-302 and MiR-372 Promote Reprogramming of Human Fibroblasts to Induced Pluripotent Stem Cells

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2011 Apr 15

PMID 21490602

Citations 311

Authors

Deepa Subramanyam

Samy Lamouille

Robert L Judson

Jason Y Liu

Nathan Bucay

Rik Derynck

Robert Blelloch

Affiliations

Soon will be listed here.

Abstract

The embryonic stem cell-specific cell cycle-regulating (ESCC) family of microRNAs (miRNAs) enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. Here we show that the human ESCC miRNA orthologs hsa-miR-302b and hsa-miR-372 promote human somatic cell reprogramming. Furthermore, these miRNAs repress multiple target genes, with downregulation of individual targets only partially recapitulating the total miRNA effects. These targets regulate various cellular processes, including cell cycle, epithelial-mesenchymal transition (EMT), epigenetic regulation and vesicular transport. ESCC miRNAs have a known role in regulating the unique embryonic stem cell cycle. We show that they also increase the kinetics of mesenchymal-epithelial transition during reprogramming and block TGFβ-induced EMT of human epithelial cells. These results demonstrate that the ESCC miRNAs promote dedifferentiation by acting on multiple downstream pathways. We propose that individual miRNAs generally act through numerous pathways that synergize to regulate and enforce cell fate decisions.

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