Hhex Is Necessary for the Hepatic Differentiation of Mouse ES Cells and Acts via Vegf Signaling

• DOI: 10.1371/journal.pone.0146806
• Publication Date: 2016-01-19T20:33:56Z
• Authors: Adam S. Arterbery; Clifford W. Bogue
• Keywords: Homeodomain Proteins; Vascular Endothelial Growth Factor A; 0303 health sciences; Science; Q; R; Cell Differentiation; Vascular Endothelial Growth Factor Receptor-2; Mice; 03 medical and health sciences; HMGB Proteins; Mutation; Hepatocyte Nuclear Factor 3-beta; Hepatocytes; SOXF Transcription Factors; Medicine; Animals; Cells, Cultured; Embryonic Stem Cells; Research Article; Transcription Factors

Elucidating the molecular mechanisms involved in differentiation of stem cells to hepatic is critical for both understanding normal developmental processes as well optimizing generation functional therapy. We performed vitro mouse embryonic (mESCs) with a null mutation homeobox gene Hhex and show that Hhex-/- mESCs fail differentiate from definitive endoderm (Sox17+/Foxa2+) (Alb+/Dlk+). In addition, culture elicited >7-fold increase Vegfa mRNA expression compared Hhex+/+ cells. Furthermore, we identified VEGFR2+/ALB+/CD34- early cultures. These were absent Finally, through manipulation expression, gain loss experiments revealed shares an inverse relationship activity Vegf signaling pathway supporting differentiation. summary, our results suggest represses during ESCs allowing cell-type autonomous regulation Vegfr2 independent endothelial