Department of Cell and Developmental Biology; Graduate School of Biomedical Sciences, Program in Cell Biology
Cell Biology | Cellular and Molecular Physiology | Developmental Biology
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.
RUNX1, SMAD2, TGFB2, cell motility, epithelial-mesenchymal transition, human embryonic stem cells, lineage commitment, mesendodermal differentiation, transcriptome profiling
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© 2016 The Authors.
DOI of Published Version
Stem Cell Reports. 2016 Nov 8;7(5):884-896. doi: 10.1016/j.stemcr.2016.09.006. Epub 2016 Oct 6. Link to article on publisher's site
Stem cell reports
VanOudenhove, Jennifer J.; Medina, Ricardo F.; Ghule, Prachi N. University of Vermont College of Medicine; Lian, Jane B.; Stein, Janet L.; Zaidi, Sayyed K.; and Stein, Gary S., "Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling" (2016). Open Access Articles. 2964.
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