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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Evolution, Molecular*
  • Hepatocytes / cytology*
  • Hepatocytes / metabolism*
  • Humans
  • Liver / cytology
  • Liver / growth & development*
  • Liver / metabolism
  • Mice
  • Mice, Inbred Strains
  • Stem Cells / cytology*
  • Stem Cells / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*


  • Vascular Endothelial Growth Factor Receptor-2