KDR identifies a conserved human and murine hepatic progenitor and instructs early liver development.

KDR identifies a conserved human and murine hepatic progenitor and instructs early liver development.
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DOI:
10.1016/j.stem.2013.04.026
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发表时间:
2013-06-06
期刊:
影响因子:
23.9
通讯作者:
Gouon-Evans, Valerie
Gouon-Evans, Valerie
中科院分区:
医学1区
文献类型:
--
作者:
Goldman, Orit;Han, Songyan;Sourrisseau, Marion;Dziedzic, Noelle;Hamou, Wissam;Corneo, Barbara;D'Souza, Sunita;Sato, Thomas;Kotton, Darrell N.;Bissig, Karl-Dimiter;Kalir, Tamara;Jacobs, Adam;Evans, Todd;Evans, Matthew J.;Gouon-Evans, Valerie

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Understanding the fetal hepatic niche is essential for optimizing the generation of functional hepatocyte-like (hepatic) cells from human embryonic stem cells (hESCs). Here, we show that KDR (VEGFR2), 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 support non-cell-autonomously the functional maturation of co-cultured 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 and subsequently adult hepatocytes and cholangiocytes. Altogether, our findings reveal that KDR is a conserved marker for endoderm-derived hepatic progenitors, and a functional receptor instructing early liver development.
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