title: Notch1 but not Notch2 is essential for generating hematopoietic stem cells from endothelial cells.
abstract: Hematopoietic stem cells (HSCs) are thought to arise in the aorta-gonad-mesonephros (AGM) region of embryo proper, although HSC activity can be detected in yolk sac (YS) and paraaortic splanchnopleura (P-Sp) when transplanted in newborn mice. We examined the role of Notch signaling in embryonic hematopoiesis. The activity of colony-forming cells in the YS from Notch1(-/-) embryos was comparable to that of wild-type embryos. However, in vitro and in vivo definitive hematopoietic activities from YS and P-Sp were severely impaired in Notch1(-/-) embryos. The population representing hemogenic endothelial cells, however, did not decrease. In contrast, Notch2(-/-) embryos showed no hematopoietic deficiency. These data indicate that Notch1, but not Notch2, is essential for generating hematopoietic stem cells from endothelial cells.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Japan.
authors.forename: Keiki
authors.initials: K
authors.lastname: Kumano
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kunisato
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Toshiki
authors.initials: T
authors.lastname: Saito
authors.forename: Etsuko
authors.initials: E
authors.lastname: Nakagami-Yamaguchi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Shigeo
authors.initials: S
authors.lastname: Masuda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shimizu
authors.forename: Tokiharu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hamada
authors.forename: Hisamaru
authors.initials: H
authors.lastname: Hirai
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014157:Transcription Factors; D015017:Yolk Sac / Q000166:cytology / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C497762:Notch1 protein, mouse; C497765:Notch2 protein, mouse; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D014157:Transcription Factors