Mesenchymal to Epithelial Transition Mediated by CDH1 Promotes Spontaneous Reprogramming of Male Germline Stem Cells to Pluripotency
Cultured spermatogonial stem cells (GSCs) can spontaneously form pluripotent cells in certain culture conditions. However, GSC reprogramming is a rare event that is largely unexplained. We show GSCs have high expression of mesenchymal to epithelial transition (MET) suppressors resulting in a develop...
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doaj-014b6ebfc9e749cd88dd232204ac63af2020-11-24T21:59:04ZengElsevierStem Cell Reports2213-67112017-02-018244645910.1016/j.stemcr.2016.12.006Mesenchymal to Epithelial Transition Mediated by CDH1 Promotes Spontaneous Reprogramming of Male Germline Stem Cells to PluripotencyJunhui An0Yu Zheng1Christina Tenenhaus Dann2Department of Chemistry, Indiana University, Chemistry A025, 800 E. Kirkwood Avenue, Bloomington, IN 47405-7102, USADepartment of Chemistry, Indiana University, Chemistry A025, 800 E. Kirkwood Avenue, Bloomington, IN 47405-7102, USADepartment of Chemistry, Indiana University, Chemistry A025, 800 E. Kirkwood Avenue, Bloomington, IN 47405-7102, USACultured spermatogonial stem cells (GSCs) can spontaneously form pluripotent cells in certain culture conditions. However, GSC reprogramming is a rare event that is largely unexplained. We show GSCs have high expression of mesenchymal to epithelial transition (MET) suppressors resulting in a developmental barrier inhibiting GSC reprogramming. Either increasing OCT4 or repressing transforming growth factor β (TGF-β) signaling promotes GSC reprogramming by upregulating CDH1 and boosting MET. Reducing ZEB1 also enhances GSC reprogramming through its direct effect on CDH1. RNA sequencing shows that rare GSCs, identified as CDH1+ after trypsin digestion, are epithelial-like cells. CDH1+ GSCs exhibit enhanced reprogramming and become more prevalent during the course of reprogramming. Our results provide a mechanistic explanation for the spontaneous emergence of pluripotent cells from GSC cultures; namely, rare GSCs upregulate CDH1 and initiate MET, processes normally kept in check by ZEB1 and TGF-β signaling, thereby ensuring germ cells are protected from aberrant acquisition of pluripotency.http://www.sciencedirect.com/science/article/pii/S221367111630296Xmale germline stem cellreprogrammingMesenchymal to epithelial transitionCDH1ZEB1TGFb signalling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Junhui An Yu Zheng Christina Tenenhaus Dann |
spellingShingle |
Junhui An Yu Zheng Christina Tenenhaus Dann Mesenchymal to Epithelial Transition Mediated by CDH1 Promotes Spontaneous Reprogramming of Male Germline Stem Cells to Pluripotency Stem Cell Reports male germline stem cell reprogramming Mesenchymal to epithelial transition CDH1 ZEB1 TGFb signalling |
author_facet |
Junhui An Yu Zheng Christina Tenenhaus Dann |
author_sort |
Junhui An |
title |
Mesenchymal to Epithelial Transition Mediated by CDH1 Promotes Spontaneous Reprogramming of Male Germline Stem Cells to Pluripotency |
title_short |
Mesenchymal to Epithelial Transition Mediated by CDH1 Promotes Spontaneous Reprogramming of Male Germline Stem Cells to Pluripotency |
title_full |
Mesenchymal to Epithelial Transition Mediated by CDH1 Promotes Spontaneous Reprogramming of Male Germline Stem Cells to Pluripotency |
title_fullStr |
Mesenchymal to Epithelial Transition Mediated by CDH1 Promotes Spontaneous Reprogramming of Male Germline Stem Cells to Pluripotency |
title_full_unstemmed |
Mesenchymal to Epithelial Transition Mediated by CDH1 Promotes Spontaneous Reprogramming of Male Germline Stem Cells to Pluripotency |
title_sort |
mesenchymal to epithelial transition mediated by cdh1 promotes spontaneous reprogramming of male germline stem cells to pluripotency |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2017-02-01 |
description |
Cultured spermatogonial stem cells (GSCs) can spontaneously form pluripotent cells in certain culture conditions. However, GSC reprogramming is a rare event that is largely unexplained. We show GSCs have high expression of mesenchymal to epithelial transition (MET) suppressors resulting in a developmental barrier inhibiting GSC reprogramming. Either increasing OCT4 or repressing transforming growth factor β (TGF-β) signaling promotes GSC reprogramming by upregulating CDH1 and boosting MET. Reducing ZEB1 also enhances GSC reprogramming through its direct effect on CDH1. RNA sequencing shows that rare GSCs, identified as CDH1+ after trypsin digestion, are epithelial-like cells. CDH1+ GSCs exhibit enhanced reprogramming and become more prevalent during the course of reprogramming. Our results provide a mechanistic explanation for the spontaneous emergence of pluripotent cells from GSC cultures; namely, rare GSCs upregulate CDH1 and initiate MET, processes normally kept in check by ZEB1 and TGF-β signaling, thereby ensuring germ cells are protected from aberrant acquisition of pluripotency. |
topic |
male germline stem cell reprogramming Mesenchymal to epithelial transition CDH1 ZEB1 TGFb signalling |
url |
http://www.sciencedirect.com/science/article/pii/S221367111630296X |
work_keys_str_mv |
AT junhuian mesenchymaltoepithelialtransitionmediatedbycdh1promotesspontaneousreprogrammingofmalegermlinestemcellstopluripotency AT yuzheng mesenchymaltoepithelialtransitionmediatedbycdh1promotesspontaneousreprogrammingofmalegermlinestemcellstopluripotency AT christinatenenhausdann mesenchymaltoepithelialtransitionmediatedbycdh1promotesspontaneousreprogrammingofmalegermlinestemcellstopluripotency |
_version_ |
1725849392089399296 |