Functional role of Mst1/Mst2 in embryonic stem cell differentiation.

The Hippo pathway is an evolutionary conserved pathway that involves cell proliferation, differentiation, apoptosis and organ size regulation. Mst1 and Mst2 are central components of this pathway that are essential for embryonic development, though their role in controlling embryonic stem cells (ES...

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Autores principales: Peng Li, Ying Chen, Kinglun Kingston Mak, Chun Kwok Wong, Chi Chiu Wang, Ping Yuan
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/fed2036ea5f0413caaceeb5d6df4de90
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spelling oai:doaj.org-article:fed2036ea5f0413caaceeb5d6df4de902021-11-18T08:48:15ZFunctional role of Mst1/Mst2 in embryonic stem cell differentiation.1932-620310.1371/journal.pone.0079867https://doaj.org/article/fed2036ea5f0413caaceeb5d6df4de902013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24224013/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The Hippo pathway is an evolutionary conserved pathway that involves cell proliferation, differentiation, apoptosis and organ size regulation. Mst1 and Mst2 are central components of this pathway that are essential for embryonic development, though their role in controlling embryonic stem cells (ES cells) has yet to be exploited. To further understand the Mst1/Mst2 function in ES cell pluripotency and differentiation, we derived Mst1/Mst2 double knockout (Mst-/-) ES cells to completely perturb Hippo signaling. We found that Mst-/- ES cells express higher level of Nanog than wild type ES cells and show differentiation resistance after LIF withdrawal. They also proliferate faster than wild type ES cells. Although Mst-/- ES cells can form embryoid bodies (EBs), their differentiation into tissues of three germ layers is distorted. Intriguingly, Mst-/- ES cells are unable to form teratoma. Mst-/- ES cells can differentiate into mesoderm lineage, but further differentiation to cardiac lineage cells is significantly affected. Microarray analysis revealed that ligands of non-canonical Wnt signaling, which is critical for cardiac progenitor specification, are significantly repressed in Mst-/- EBs. Taken together our results showed that Mst1/Mst2 are required for proper cardiac lineage cell development and teratoma formation.Peng LiYing ChenKinglun Kingston MakChun Kwok WongChi Chiu WangPing YuanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79867 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Peng Li
Ying Chen
Kinglun Kingston Mak
Chun Kwok Wong
Chi Chiu Wang
Ping Yuan
Functional role of Mst1/Mst2 in embryonic stem cell differentiation.
description The Hippo pathway is an evolutionary conserved pathway that involves cell proliferation, differentiation, apoptosis and organ size regulation. Mst1 and Mst2 are central components of this pathway that are essential for embryonic development, though their role in controlling embryonic stem cells (ES cells) has yet to be exploited. To further understand the Mst1/Mst2 function in ES cell pluripotency and differentiation, we derived Mst1/Mst2 double knockout (Mst-/-) ES cells to completely perturb Hippo signaling. We found that Mst-/- ES cells express higher level of Nanog than wild type ES cells and show differentiation resistance after LIF withdrawal. They also proliferate faster than wild type ES cells. Although Mst-/- ES cells can form embryoid bodies (EBs), their differentiation into tissues of three germ layers is distorted. Intriguingly, Mst-/- ES cells are unable to form teratoma. Mst-/- ES cells can differentiate into mesoderm lineage, but further differentiation to cardiac lineage cells is significantly affected. Microarray analysis revealed that ligands of non-canonical Wnt signaling, which is critical for cardiac progenitor specification, are significantly repressed in Mst-/- EBs. Taken together our results showed that Mst1/Mst2 are required for proper cardiac lineage cell development and teratoma formation.
format article
author Peng Li
Ying Chen
Kinglun Kingston Mak
Chun Kwok Wong
Chi Chiu Wang
Ping Yuan
author_facet Peng Li
Ying Chen
Kinglun Kingston Mak
Chun Kwok Wong
Chi Chiu Wang
Ping Yuan
author_sort Peng Li
title Functional role of Mst1/Mst2 in embryonic stem cell differentiation.
title_short Functional role of Mst1/Mst2 in embryonic stem cell differentiation.
title_full Functional role of Mst1/Mst2 in embryonic stem cell differentiation.
title_fullStr Functional role of Mst1/Mst2 in embryonic stem cell differentiation.
title_full_unstemmed Functional role of Mst1/Mst2 in embryonic stem cell differentiation.
title_sort functional role of mst1/mst2 in embryonic stem cell differentiation.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/fed2036ea5f0413caaceeb5d6df4de90
work_keys_str_mv AT pengli functionalroleofmst1mst2inembryonicstemcelldifferentiation
AT yingchen functionalroleofmst1mst2inembryonicstemcelldifferentiation
AT kinglunkingstonmak functionalroleofmst1mst2inembryonicstemcelldifferentiation
AT chunkwokwong functionalroleofmst1mst2inembryonicstemcelldifferentiation
AT chichiuwang functionalroleofmst1mst2inembryonicstemcelldifferentiation
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