Notch1 but not Notch2 is essential for generating hematopoietic stem cells from endothelial cells.
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.
Kumano
Keiki
K
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Japan.
Chiba
Shigeru
S
Kunisato
Atsushi
A
Sata
Masataka
M
Saito
Toshiki
T
Nakagami-Yamaguchi
Etsuko
E
Yamaguchi
Tomoyuki
T
Masuda
Shigeo
S
Shimizu
Kiyoshi
K
Takahashi
Tokiharu
T
Ogawa
Seishi
S
Hamada
Yoshio
Y
Hirai
Hisamaru
H
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
D008565:Membrane Proteins; C497762:Notch1 protein, mouse; C497765:Notch2 protein, mouse; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D014157:Transcription Factors