Endomucin, a CD34-like sialomucin, marks hematopoietic stem cells throughout development.
To detect as yet unidentified cell-surface molecules specific to hematopoietic stem cells (HSCs), a modified signal sequence trap was successfully applied to mouse bone marrow (BM) CD34(-)c-Kit(+)Sca-1(+)Lin(-) (CD34(-)KSL) HSCs. One of the identified molecules, Endomucin, is an endothelial sialomucin closely related to CD34. High-level expression of Endomucin was confined to the BM KSL HSCs and progenitor cells, and, importantly, long-term repopulating (LTR)-HSCs were exclusively present in the Endomucin(+)CD34(-)KSL population. Notably, in the yolk sac, Endomucin expression separated multipotential hematopoietic cells from committed erythroid progenitors in the cell fraction positive for CD41, an early embryonic hematopoietic marker. Furthermore, developing HSCs in the intraembryonic aorta-gonad-mesonephros (AGM) region were highly enriched in the CD45(-)CD41(+)Endomucin(+) fraction at day 10.5 of gestation (E10.5) and in the CD45(+)CD41(+)Endomucin(+) fraction at E11.5. Detailed analyses of these fractions uncovered drastic changes in their BM repopulating capacities as well as in vitro cytokine responsiveness within this narrow time frame. Our findings establish Endomucin as a novel cell-surface marker for LTR-HSCs throughout development and provide a powerful tool in understanding HSC ontogeny.
Matsubara
Azusa
A
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Iwama
Atsushi
A
Yamazaki
Satoshi
S
Furuta
Chie
C
Hirasawa
Ryutaro
R
Morita
Yohei
Y
Osawa
Mitsujiro
M
Motohashi
Tsutomu
T
Eto
Koji
K
Ema
Hideo
H
Kitamura
Toshio
T
Vestweber
Dietmar
D
Nakauchi
Hiromitsu
H
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D001011:Aorta / Q000196:embryology; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage / Q000502:physiology; D006066:Gonads / Q000196:embryology; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells; D008650:Mesonephros / Q000196:embryology*; D051379:Mice; D008815:Mice, Inbred Strains; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D052116:Sialomucins / Q000276:immunology*; D015017:Yolk Sac / Q000196:embryology*
D018952:Antigens, CD34; D015415:Biomarkers; C498985:Emcn protein, mouse; D012795:Sialoglycoproteins; D052116:Sialomucins