The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances Reprogramming
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) p...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-11-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671114002938 |
| _version_ | 1828445156058071040 |
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| author | Juli J. Unternaehrer Rui Zhao Kitai Kim Marcella Cesana John T. Powers Sutheera Ratanasirintrawoot Tamer Onder Tsukasa Shibue Robert A. Weinberg George Q. Daley |
| author_facet | Juli J. Unternaehrer Rui Zhao Kitai Kim Marcella Cesana John T. Powers Sutheera Ratanasirintrawoot Tamer Onder Tsukasa Shibue Robert A. Weinberg George Q. Daley |
| author_sort | Juli J. Unternaehrer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T21:53:36Z |
| format | Article |
| id | doaj.art-2ceafcf7bcea42f9b4f7de18552eddaf |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-10T21:53:36Z |
| publishDate | 2014-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-2ceafcf7bcea42f9b4f7de18552eddaf2022-12-22T01:32:06ZengElsevierStem Cell Reports2213-67112014-11-013569169810.1016/j.stemcr.2014.09.008The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances ReprogrammingJuli J. Unternaehrer0Rui Zhao1Kitai Kim2Marcella Cesana3John T. Powers4Sutheera Ratanasirintrawoot5Tamer Onder6Tsukasa Shibue7Robert A. Weinberg8George Q. Daley9Division 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, USADivision 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, USADivision 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, USADivision 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, USADivision 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, USADivision 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, USADivision 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, USAWhitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USAWhitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USADivision 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, USAReprogramming 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.http://www.sciencedirect.com/science/article/pii/S2213671114002938 |
| spellingShingle | Juli J. Unternaehrer Rui Zhao Kitai Kim Marcella Cesana John T. Powers Sutheera Ratanasirintrawoot Tamer Onder Tsukasa Shibue Robert A. Weinberg George Q. Daley The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances Reprogramming Stem Cell Reports |
| title | The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances Reprogramming |
| title_full | The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances Reprogramming |
| title_fullStr | The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances Reprogramming |
| title_full_unstemmed | The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances Reprogramming |
| title_short | The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances Reprogramming |
| title_sort | epithelial mesenchymal transition factor snail paradoxically enhances reprogramming |
| url | http://www.sciencedirect.com/science/article/pii/S2213671114002938 |
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