Stem Cell Reports | |
Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling | |
Jane B. Lian1  Sayyed K. Zaidi1  Jennifer J. VanOudenhove1  Janet L. Stein1  Prachi N. Ghule1  Gary S. Stein1  Ricardo Medina2  | |
[1] Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington, VT 05405, USA;Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA; | |
关键词: RUNX1; TGFB2; SMAD2; epithelial-mesenchymal transition; mesendodermal differentiation; human embryonic stem cells; lineage commitment; cell motility; transcriptome profiling; | |
DOI : 10.1016/j.stemcr.2016.09.006 | |
来源: DOAJ |
【 摘 要 】
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.
【 授权许可】
Unknown