Notch1 but not Notch2 is essential for generating hematopoietic stem cells from endothelial cells

Keiki Kumano, Shigeru Chiba, Atsushi Kunisato, Masataka Sata, Toshiki Saito, Etsuko Nakagami-Yamaguchi, Tomoyuki Yamaguchi, Shigeo Masuda, Kiyoshi Shimizu, Tokiharu Takahashi, Seishi Ogawa, Yoshio Hamada, Hisamaru Hirai

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)699-711
    Number of pages12
    JournalImmunity
    Volume18
    Issue number5
    DOIs
    Publication statusPublished - 1 May 2003

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