title: alpha4-Integrin(+) endothelium derived from primate embryonic stem cells generates primitive and definitive hematopoietic cells.
abstract: The mechanism of commencement of hematopoiesis in blood islands of the yolk sac and the aorta-gonad-mesonephros (AGM) region during primate embryogenesis remains elusive. In this study, we demonstrated that VE-cadherin(+)CD45(-) endothelial cells derived from nonhuman primate embryonic stem cells are able to generate primitive and definitive hematopoietic cells sequentially, as revealed by immunostaining of floating erythrocytes and colony-forming assay in cultures. Single bipotential progenitors for hematopoietic and endothelial lineages are included in this endothelial cell population. Furthermore, hemogenic activity of these endothelial cells is observed exclusively in the alpha4-integrin(+) subpopulation; bipotential progenitors are 4-fold enriched in this subpopulation. The kinetics of this hemogenic subpopulation is similar to that of hemogenic endothelial cells previously reported in the yolk sac and the AGM region in vivo in that they emerge for only a limited time. We suggest that VE-cadherin(+)CD45(-)alpha4-integrin(+) endothelial cells are involved in primitive and definitive hematopoiesis during primate embryogenesis, though VE-cadherin(-)CD45(-)alpha4-integrin(+) cells are the primary sources for primitive hematopoiesis.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Shinoda
authors.forename: Katsutsugu
authors.initials: K
authors.lastname: Umeda
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Masato
authors.initials: M
authors.lastname: Arai
authors.forename: Akira
authors.initials: A
authors.lastname: Niwa
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Suemori
authors.forename: Hong Yuan
authors.initials: HY
authors.lastname: Luo
authors.forename: David H K
authors.initials: DH
authors.lastname: Chui
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Torii
authors.forename: Masabumi
authors.initials: M
authors.lastname: Shibuya
authors.forename: Norio
authors.initials: N
authors.lastname: Nakatsuji
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D006410:Hematopoiesis; D039441:Integrin alpha4 / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008252:Macaca fascicularis; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D039441:Integrin alpha4; D017493:Leukocyte Common Antigens; D000099152:Cadherin 5