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

First Author  Goldman O Year  2013
Journal  Cell Stem Cell Volume  12
Issue  6 Pages  748-60
PubMed ID  23746980 Mgi Jnum  J:315741
Mgi Id  MGI:6830036 Doi  10.1016/j.stem.2013.04.026
Citation  Goldman O, et al. (2013) KDR identifies a conserved human and murine hepatic progenitor and instructs early liver development. Cell Stem Cell 12(6):748-60
abstractText  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.
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