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Cell Stem Cell. 2013 Jun 6;12(6):748-60. doi: 10.1016/j.stem.2013.04.026.

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

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1
Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Erratum in

  • Cell Stem Cell. 2013 Dec 5;13(6):769. Sourrisseau, Marion [corrected to Sourisseau,].

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.

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PMID:
23746980
PMCID:
PMC3922205
DOI:
10.1016/j.stem.2013.04.026
[Indexed for MEDLINE]
Free PMC Article
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