Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2017 Nov 28

PMID 29174331

Citations 27

Authors

Tyson Ruetz

Ulrich Pfisterer

Bruno Di Stefano

James Ashmore

Meryam Beniazza

Tian V Tian

Daniel F Kaemena

Luca Tosti

Wenfang Tan

Jonathan R Manning

Eleni Chantzoura

Daniella Rylander Ottosson

Samuel Collombet

Anna Johnsson

Erez Cohen

Kosuke Yusa

Sten Linnarsson

Thomas Graf

Malin Parmar

Keisuke Kaji

Affiliations

Soon will be listed here.

Abstract

Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine. However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells. Here, we show that expression of constitutively active SMAD2/3 significantly improves the efficiency of induced pluripotent stem cell (iPSC) generation by the Yamanaka factors. Mechanistically, SMAD3 interacts with reprogramming factors and co-activators and co-occupies OCT4 target loci during reprogramming. Unexpectedly, active SMAD2/3 also markedly enhances three other TF-mediated direct reprogramming conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons, highlighting broad and general roles for SMAD2/3 as cell-reprogramming potentiators. Our results suggest that co-expression of active SMAD2/3 could enhance multiple types of TF-based cell identity conversion and therefore be a powerful tool for cellular engineering.

Citing Articles

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