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The epithelial-mesenchymal transition factor SNAIL paradoxically enhances reprogramming.

Abstract：

:Reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) entails a mesenchymal to epithelial transition (MET). While attempting to dissect the mechanism of MET during reprogramming, we observed that knockdown (KD) of the epithelial-to-mesenchymal transition (EMT) factor SNAI1 (SNAIL) paradoxically reduced, while overexpression enhanced, reprogramming efficiency in human cells and in mouse cells, depending on strain. We observed nuclear localization of SNAI1 at an early stage of fibroblast reprogramming and using mouse fibroblasts expressing a knockin SNAI1-YFP reporter found cells expressing SNAI1 reprogrammed at higher efficiency. We further demonstrated that SNAI1 binds the let-7 promoter, which may play a role in reduced expression of let-7 microRNAs, enforced expression of which, early in the reprogramming process, compromises efficiency. Our data reveal an unexpected role for the EMT factor SNAI1 in reprogramming somatic cells to pluripotency.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Unternaehrer JJ,Zhao R,Kim K,Cesana M,Powers JT,Ratanasirintrawoot S,Onder T,Shibue T,Weinberg RA,Daley GQ

doi

10.1016/j.stemcr.2014.09.008

subject

Has Abstract

pub_date

2014-11-11 00:00:00

pages

691-8

issue

5

issn

2213-6711

pii

S2213-6711(14)00293-8

journal_volume

3

pub_type

杂志文章

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