KDR Identifies a Conserved Human and Murine Hepatic Progenitor and Instructs Early Liver Development - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Journal Articles Cell Stem Cell Year : 2013

KDR Identifies a Conserved Human and Murine Hepatic Progenitor and Instructs Early Liver Development

Abstract

Understanding the fetal hepatic niche is essential for optimizing the generation of functional hepatocyte-like cells (hepatic cells) from human embryonic stem cells (hESCs). Here, we show that KDR (VEGFR2/FLK-1), previously assumed to be mostly restricted to mesodermal lineages, marks a hESC-derived hepatic progenitor. hESC-derived endoderm cells do not express KDR but, when cultured in media supporting hepatic differentiation, generate KDR+ hepatic progenitors and KDR- hepatic cells. KDR+ progenitors require active KDR signaling both to instruct their own differentiation into hepatic cells and to non-cell-autonomously support the functional maturation of cocultured KDR- hepatic cells. Analysis of human fetal livers suggests that similar progenitors are present in human livers. Lineage tracing in mice provides in vivo evidence of a KDR+ hepatic progenitor for fetal hepatoblasts, adult hepatocytes, and adult cholangiocytes. Altogether, our findings reveal that KDR is a conserved marker for endoderm-derived hepatic progenitors and a functional receptor instructing early liver development.

Dates and versions

hal-04181119 , version 1 (14-08-2023)

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Orit Goldman, Songyan Han, Marion Sourisseau, Noelle Dziedzic, Wissam Hamou, et al.. KDR Identifies a Conserved Human and Murine Hepatic Progenitor and Instructs Early Liver Development. Cell Stem Cell, 2013, 12 (6), pp.748-760. ⟨10.1016/j.stem.2013.04.026⟩. ⟨hal-04181119⟩

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