title: Endoderm generates endothelial cells during liver development.
abstract: Organogenesis requires expansion of the embryonic vascular plexus that migrates into developing organs through a process called angiogenesis. Mesodermal progenitors are thought to derive endothelial cells (ECs) that contribute to both embryonic vasculogenesis and the subsequent organ angiogenesis. Here, we demonstrate that during development of the liver, which is an endoderm derivative, a subset of ECs is generated from FOXA2+ endoderm-derived fetal hepatoblast progenitor cells expressing KDR (VEGFR2/FLK-1). Using human and mouse embryonic stem cell models, we demonstrate that KDR+FOXA2+ endoderm cells developing in hepatic differentiation cultures generate functional ECs. This introduces the concept that ECs originate not exclusively from mesoderm but also from endoderm, supported in Foxa2 lineage-tracing mouse embryos by the identification of FOXA2+ cell-derived CD31+ ECs that integrate the vascular network of developing fetal livers.
authors.affiliation: Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine, Mount Sinai, New York, NY 10029, USA.
authors.forename: Orit
authors.initials: O
authors.lastname: Goldman
authors.affiliation: Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine, Mount Sinai, New York, NY 10029, USA.
authors.forename: Songyan
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine, Mount Sinai, New York, NY 10029, USA.
authors.forename: Wissam
authors.initials: W
authors.lastname: Hamou
authors.affiliation: INSERM U972, Hospital Paul Brousse, 12 Avenue Paul Vaillant Couturier, 94807 Villejuif, France.
authors.forename: Vanina
authors.initials: V
authors.lastname: Jodon de Villeroche
authors.affiliation: INSERM U972, Hospital Paul Brousse, 12 Avenue Paul Vaillant Couturier, 94807 Villejuif, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Uzan
authors.affiliation: Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Lickert
authors.affiliation: Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine, Mount Sinai, New York, NY 10029, USA. Electronic address: valerie.gouon-evans@mssm.edu.
authors.forename: Valerie
authors.initials: V
authors.lastname: Gouon-Evans
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004707:Endoderm / Q000166:cytology*; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000196:embryology; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: C496503:Foxa2 protein, mouse; D051542:Hepatocyte Nuclear Factor 3-beta; D040301:Vascular Endothelial Growth Factor Receptor-2