title: Identification of the hemogenic endothelial progenitor and its direct precursor in human pluripotent stem cell differentiation cultures.
abstract: Hemogenic endothelium (HE) has been recognized as a source of hematopoietic stem cells (HSCs) in the embryo. Access to human HE progenitors (HEPs) is essential for enabling the investigation of the molecular determinants of HSC specification. Here, we show that HEPs capable of generating definitive hematopoietic cells can be obtained from human pluripotent stem cells (hPSCs) and identified precisely by a VE-cadherin(+)CD73(-)CD235a/CD43(-) phenotype. This phenotype discriminates true HEPs from VE-cadherin(+)CD73(+) non-HEPs and VE-cadherin(+)CD235a(+)CD41a(-) early hematopoietic cells with endothelial and FGF2-dependent hematopoietic colony-forming potential. We found that HEPs arise at the post-primitive-streak stage of differentiation directly from VE-cadherin-negative KDR(bright)APLNR(+)PDGFRα(low/-) hematovascular mesodermal precursors (HVMPs). In contrast, hemangioblasts, which are capable of forming endothelium and primitive blood cells, originate from more immature APLNR(+)PDGFRα(+) mesoderm. The demarcation of HEPs and HVMPs provides a platform for modeling blood development from endothelium with a goal of facilitating the generation of HSCs from hPSCs.
authors.affiliation: National Primate Research Center, University of Wisconsin Graduate School, Madison, WI 53715, USA.
authors.forename: Kyung-Dal
authors.initials: KD
authors.lastname: Choi
authors.forename: Maxim A
authors.initials: MA
authors.lastname: Vodyanik
authors.forename: Padma Priya
authors.initials: PP
authors.lastname: Togarrati
authors.forename: Kran
authors.initials: K
authors.lastname: Suknuntha
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Kumar
authors.forename: Fnu
authors.initials: F
authors.lastname: Samarjeet
authors.forename: Mitchell D
authors.initials: MD
authors.lastname: Probasco
authors.forename: Shulan
authors.initials: S
authors.lastname: Tian
authors.forename: Ron
authors.initials: R
authors.lastname: Stewart
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
authors.forename: Igor I
authors.initials: II
authors.lastname: Slukvin
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D055018:Hemangioblasts / Q000166:cytology / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D016222:Fibroblast Growth Factor 2; D000099152:Cadherin 5