TY - JOUR
T1 - KDR identifies a conserved human and murine hepatic progenitor and instructs early liver development
AU - Goldman, Orit
AU - Han, Songyan
AU - Sourrisseau, Marion
AU - Dziedzic, Noelle
AU - Hamou, Wissam
AU - Corneo, Barbara
AU - D'Souza, Sunita
AU - Sato, Thomas
AU - Kotton, Darrell N.
AU - Bissig, Karl Dimiter
AU - Kalir, Tamara
AU - Jacobs, Adam
AU - Evans, Todd
AU - Evans, Matthew J.
AU - Gouon-Evans, Valerie
N1 - Funding Information:
This work was supported by the Black Family Stem Cell Institute, the National Institute of Diabetes and Digestive and Kidney Diseases for the mouse study (R01DK087867-01 to V.G.E.), the Robin Chemers Neustein Postdoctoral Fellowship (M.S.), the American Cancer Society (RSG-12-176-01-MPC to M.J.E.), and the Pew Charitable Funds (M.J.E.).
PY - 2013/6/6
Y1 - 2013/6/6
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84878831119
U2 - 10.1016/j.stem.2013.04.026
DO - 10.1016/j.stem.2013.04.026
M3 - Article
C2 - 23746980
AN - SCOPUS:84878831119
SN - 1934-5909
VL - 12
SP - 748
EP - 760
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 6
ER -