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.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Goldman O,Han S,Sourisseau M,Dziedzic N,Hamou W,Corneo B,D'Souza S,Sato T,Kotton DN,Bissig KD,Kalir T,Jacobs A,Evans T,Evans MJ,Gouon-Evans Vdoi
10.1016/j.stem.2013.04.026subject
Has Abstractpub_date
2013-06-06 00:00:00pages
748-60issue
6eissn
1934-5909issn
1875-9777pii
S1934-5909(13)00193-8journal_volume
12pub_type
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