Sequential EMT-MET Induces Neuronal Conversion Through Sox2

Overview

Journal Cell Discov

Date 2017 Jun 6

PMID 28580167

Citations 13

Authors

Songwei He

Jinlong Chen

Yixin Zhang

Mengdan Zhang

Xiao Yang

Yuan Li

Hao Sun

Lilong Lin

Ke Fan

Lining Liang

Chengqian Feng

Fuhui Wang

Xiao Zhang

Yiping Guo

Duanqing Pei

Hui Zheng

Affiliations

Soon will be listed here.

Abstract

Direct neuronal conversion can be achieved with combinations of small-molecule compounds and growth factors. Here, by studying the first or induction phase of the neuronal conversion induced by defined 5C medium, we show that the Sox2-mediated switch from early epithelial-mesenchymal transition (EMT) to late mesenchymal-epithelial transition (MET) within a high proliferation context is essential and sufficient for the conversion from mouse embryonic fibroblasts (MEFs) to TuJ cells. At the early stage, insulin and basic fibroblast growth factor (bFGF)-induced cell proliferation, early EMT, the up-regulation of and , and the subsequent activation of neuron projection. Up-regulated then induced MET and directed cells towards a neuronal fate at the late stage. Inhibiting either stage of this sequential EMT-MET impaired the conversion. In addition, Sox2 could replace sequential EMT-MET to induce a similar conversion within a high proliferation context, and its functions were confirmed with other neuronal conversion protocols and MEFs reprogramming. Therefore, the critical roles of the sequential EMT-MET were implicated in direct cell fate conversion in addition to reprogramming, embryonic development and cancer progression.

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