The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances Reprogramming

Juli J. Unternaehrer; Rui Zhao; Kitai Kim; Marcella Cesana; John T. Powers; Sutheera Ratanasirintrawoot; Tamer Onder; Tsukasa Shibue; Robert A. Weinberg; George Q. Daley

doi:10.1016/j.stemcr.2014.09.008

Stem Cell Reports (Nov 2014)

The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances Reprogramming

Juli J. Unternaehrer,
Rui Zhao,
Kitai Kim,
Marcella Cesana,
John T. Powers,
Sutheera Ratanasirintrawoot,
Tamer Onder,
Tsukasa Shibue,
Robert A. Weinberg,
George Q. Daley

Affiliations

Juli J. Unternaehrer: Division of Pediatric Hematology/Oncology, Stem Cell Transplantation Program, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children’s Hospital Boston and Dana Farber Cancer Institute, Harvard University, Cambridge, MA 02138, USA
Rui Zhao: Division of Pediatric Hematology/Oncology, Stem Cell Transplantation Program, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children’s Hospital Boston and Dana Farber Cancer Institute, Harvard University, Cambridge, MA 02138, USA
Kitai Kim: Division of Pediatric Hematology/Oncology, Stem Cell Transplantation Program, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children’s Hospital Boston and Dana Farber Cancer Institute, Harvard University, Cambridge, MA 02138, USA
Marcella Cesana: Division of Pediatric Hematology/Oncology, Stem Cell Transplantation Program, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children’s Hospital Boston and Dana Farber Cancer Institute, Harvard University, Cambridge, MA 02138, USA
John T. Powers: Division of Pediatric Hematology/Oncology, Stem Cell Transplantation Program, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children’s Hospital Boston and Dana Farber Cancer Institute, Harvard University, Cambridge, MA 02138, USA
Sutheera Ratanasirintrawoot: Division of Pediatric Hematology/Oncology, Stem Cell Transplantation Program, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children’s Hospital Boston and Dana Farber Cancer Institute, Harvard University, Cambridge, MA 02138, USA
Tamer Onder: Division of Pediatric Hematology/Oncology, Stem Cell Transplantation Program, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children’s Hospital Boston and Dana Farber Cancer Institute, Harvard University, Cambridge, MA 02138, USA
Tsukasa Shibue: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
Robert A. Weinberg: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
George Q. Daley: Division of Pediatric Hematology/Oncology, Stem Cell Transplantation Program, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children’s Hospital Boston and Dana Farber Cancer Institute, Harvard University, Cambridge, MA 02138, USA

DOI: https://doi.org/10.1016/j.stemcr.2014.09.008
Journal volume & issue: Vol. 3, no. 5
pp. 691 – 698

Abstract

Read online

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.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

About the journal