Authors:
Orit Goldman, Songyan Han, Marion Sourrisseau, Noelle Dziedzic, Wissam Hamou, Barbara Corneo, Sunita DSouza, Thomas Sato, Darrell N. Kotton, Karl-Dimiter Bissig, Tamara Kalir, Adam Jacobs, Todd Evans, Matthew J. Evans, & Valerie Gouon-Evans
Summary:
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.
Source:
Cell Stem Cell; Vol. 12, Issue 6, 748-760 (06/06/13)