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Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling

The transition of human embryonic stem cells (hESCs) from pluripotency to lineage commitment is not fully understood, and a role for phenotypic transcription factors in the initial stages of hESC differentiation remains to be explored. From a screen of candidate factors, we found that RUNX1 is selec...

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Autores principales: VanOudenhove, Jennifer J., Medina, Ricardo, Ghule, Prachi N., Lian, Jane B., Stein, Janet L., Zaidi, Sayyed K., Stein, Gary S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106514/
https://www.ncbi.nlm.nih.gov/pubmed/27720906
http://dx.doi.org/10.1016/j.stemcr.2016.09.006
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author VanOudenhove, Jennifer J.
Medina, Ricardo
Ghule, Prachi N.
Lian, Jane B.
Stein, Janet L.
Zaidi, Sayyed K.
Stein, Gary S.
author_facet VanOudenhove, Jennifer J.
Medina, Ricardo
Ghule, Prachi N.
Lian, Jane B.
Stein, Janet L.
Zaidi, Sayyed K.
Stein, Gary S.
author_sort VanOudenhove, Jennifer J.
collection PubMed
description The transition of human embryonic stem cells (hESCs) from pluripotency to lineage commitment is not fully understood, and a role for phenotypic transcription factors in the initial stages of hESC differentiation remains to be explored. From a screen of candidate factors, we found that RUNX1 is selectively and transiently upregulated early in hESC differentiation to mesendodermal lineages. Transcriptome profiling and functional analyses upon RUNX1 depletion established a role for RUNX1 in promoting cell motility. In parallel, we discovered a loss of repression for several epithelial genes, indicating that loss of RUNX1 impaired an epithelial to mesenchymal transition during differentiation. Cell biological and biochemical approaches revealed that RUNX1 depletion specifically compromised TGFB2 signaling. Both the decrease in motility and deregulated epithelial marker expression upon RUNX1 depletion were rescued by reintroduction of TGFB2, but not TGFB1. These findings identify roles for RUNX1-TGFB2 signaling in early events of mesendodermal lineage commitment.
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spelling pubmed-51065142016-11-17 Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling VanOudenhove, Jennifer J. Medina, Ricardo Ghule, Prachi N. Lian, Jane B. Stein, Janet L. Zaidi, Sayyed K. Stein, Gary S. Stem Cell Reports Article The transition of human embryonic stem cells (hESCs) from pluripotency to lineage commitment is not fully understood, and a role for phenotypic transcription factors in the initial stages of hESC differentiation remains to be explored. From a screen of candidate factors, we found that RUNX1 is selectively and transiently upregulated early in hESC differentiation to mesendodermal lineages. Transcriptome profiling and functional analyses upon RUNX1 depletion established a role for RUNX1 in promoting cell motility. In parallel, we discovered a loss of repression for several epithelial genes, indicating that loss of RUNX1 impaired an epithelial to mesenchymal transition during differentiation. Cell biological and biochemical approaches revealed that RUNX1 depletion specifically compromised TGFB2 signaling. Both the decrease in motility and deregulated epithelial marker expression upon RUNX1 depletion were rescued by reintroduction of TGFB2, but not TGFB1. These findings identify roles for RUNX1-TGFB2 signaling in early events of mesendodermal lineage commitment. Elsevier 2016-10-06 /pmc/articles/PMC5106514/ /pubmed/27720906 http://dx.doi.org/10.1016/j.stemcr.2016.09.006 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
VanOudenhove, Jennifer J.
Medina, Ricardo
Ghule, Prachi N.
Lian, Jane B.
Stein, Janet L.
Zaidi, Sayyed K.
Stein, Gary S.
Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling
title Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling
title_full Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling
title_fullStr Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling
title_full_unstemmed Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling
title_short Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling
title_sort transient runx1 expression during early mesendodermal differentiation of hescs promotes epithelial to mesenchymal transition through tgfb2 signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106514/
https://www.ncbi.nlm.nih.gov/pubmed/27720906
http://dx.doi.org/10.1016/j.stemcr.2016.09.006
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