UMMS Affiliation

Department of Cell and Developmental Biology; Graduate School of Biomedical Sciences, Program in Cell Biology

Date

11-8-2016

Document Type

Article

Disciplines

Cell Biology | Cellular and Molecular Physiology | Developmental Biology

Abstract

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.

Rights and Permissions

© 2016 The Authors.

Source

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

Related Resources

Link to Article in PubMed

Keywords

RUNX1, SMAD2, TGFB2, cell motility, epithelial-mesenchymal transition, human embryonic stem cells, lineage commitment, mesendodermal differentiation, transcriptome profiling

Journal Title

Stem cell reports

PubMed ID

27720906

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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