PMID- 25316190 OWN - NLM STAT- MEDLINE DCOM- 20150720 LR - 20211021 IS - 2213-6711 (Electronic) IS - 2213-6711 (Linking) VI - 3 IP - 5 DP - 2014 Nov 11 TI - The epithelial-mesenchymal transition factor SNAIL paradoxically enhances reprogramming. PG - 691-8 LID - S2213-6711(14)00293-8 [pii] LID - 10.1016/j.stemcr.2014.09.008 [doi] AB - 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. CI - Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Unternaehrer, Juli J AU - Unternaehrer JJ AD - 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; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: junternaehrer@llu.edu. FAU - Zhao, Rui AU - Zhao R AD - 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; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. FAU - Kim, Kitai AU - Kim K AD - 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; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. FAU - Cesana, Marcella AU - Cesana M AD - 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; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. FAU - Powers, John T AU - Powers JT AD - 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; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. FAU - Ratanasirintrawoot, Sutheera AU - Ratanasirintrawoot S AD - 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; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. FAU - Onder, Tamer AU - Onder T AD - 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; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. FAU - Shibue, Tsukasa AU - Shibue T AD - Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. FAU - Weinberg, Robert A AU - Weinberg RA AD - Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. FAU - Daley, George Q AU - Daley GQ AD - 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; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. LA - eng GR - R01 GM107536/GM/NIGMS NIH HHS/United States GR - T32 HL007623/HL/NHLBI NIH HHS/United States GR - T32-HL07623-23/HL/NHLBI NIH HHS/United States GR - R01-GM107536/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20141011 PL - United States TA - Stem Cell Reports JT - Stem cell reports JID - 101611300 RN - 0 (Luminescent Proteins) RN - 0 (MicroRNAs) RN - 0 (SNAI1 protein, human) RN - 0 (Snai1 protein, mouse) RN - 0 (Snail Family Transcription Factors) RN - 0 (Transcription Factors) RN - 0 (mirnlet7 microRNA, mouse) SB - IM MH - Animals MH - Animals, Newborn MH - Cell Differentiation/genetics MH - Cells, Cultured MH - Cellular Reprogramming/*genetics MH - Epithelial-Mesenchymal Transition/*genetics MH - Fibroblasts/cytology/metabolism MH - Gene Expression MH - Humans MH - Induced Pluripotent Stem Cells/cytology/*metabolism MH - Keratinocytes/cytology/metabolism MH - Luminescent Proteins/genetics/metabolism MH - Mice, 129 Strain MH - Mice, Inbred C57BL MH - MicroRNAs/genetics/metabolism MH - Microscopy, Confocal MH - Promoter Regions, Genetic/genetics MH - Protein Binding MH - RNA Interference MH - Reverse Transcriptase Polymerase Chain Reaction MH - Snail Family Transcription Factors MH - Transcription Factors/*genetics/metabolism PMC - PMC4235745 EDAT- 2014/10/16 06:00 MHDA- 2015/07/21 06:00 PMCR- 2014/10/11 CRDT- 2014/10/16 06:00 PHST- 2013/05/27 00:00 [received] PHST- 2014/09/09 00:00 [revised] PHST- 2014/09/09 00:00 [accepted] PHST- 2014/10/16 06:00 [entrez] PHST- 2014/10/16 06:00 [pubmed] PHST- 2015/07/21 06:00 [medline] PHST- 2014/10/11 00:00 [pmc-release] AID - S2213-6711(14)00293-8 [pii] AID - 10.1016/j.stemcr.2014.09.008 [doi] PST - ppublish SO - Stem Cell Reports. 2014 Nov 11;3(5):691-8. doi: 10.1016/j.stemcr.2014.09.008. Epub 2014 Oct 11.