title: KDR identifies a conserved human and murine hepatic progenitor and instructs early liver development.
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.
authors.affiliation: Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Orit
authors.initials: O
authors.lastname: Goldman
authors.forename: Songyan
authors.initials: S
authors.lastname: Han
authors.forename: Marion
authors.initials: M
authors.lastname: Sourisseau
authors.forename: Marion
authors.initials: M
authors.lastname: Sourrisseau
authors.forename: Noelle
authors.initials: N
authors.lastname: Dziedzic
authors.forename: Wissam
authors.initials: W
authors.lastname: Hamou
authors.forename: Barbara
authors.initials: B
authors.lastname: Corneo
authors.forename: Sunita
authors.initials: S
authors.lastname: D'Souza
authors.forename: Thomas
authors.initials: T
authors.lastname: Sato
authors.forename: Darrell N
authors.initials: DN
authors.lastname: Kotton
authors.forename: Karl-Dimiter
authors.initials: KD
authors.lastname: Bissig
authors.forename: Tamara
authors.initials: T
authors.lastname: Kalir
authors.forename: Adam
authors.initials: A
authors.lastname: Jacobs
authors.forename: Todd
authors.initials: T
authors.lastname: Evans
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Evans
authors.forename: Valerie
authors.initials: V
authors.lastname: Gouon-Evans
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2