The Journal of Experimental Medicine
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Published online 28 November 2005 doi:10.1084/jem.20051325
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 11, 1483-1492
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ARTICLE

 Endomucin, a CD34-like sialomucin, marks hematopoietic stem cells throughout development

Azusa Matsubara1, Atsushi Iwama1,6, Satoshi Yamazaki1,7, Chie Furuta1, Ryutaro Hirasawa1, Yohei Morita1,7, Mitsujiro Osawa1, Tsutomu Motohashi4, Koji Eto1, Hideo Ema1, Toshio Kitamura2,3, Dietmar Vestweber5, and Hiromitsu Nakauchi1

1 Laboratory of Stem Cell Therapy, Center for Experimental Medicine
2 Division of Cellular Therapy, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
3 Division of Hematopoietic Factors, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
4 Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 500, Japan
5 Institute of Cell Biology, Center for Molecular Biology of Inflammation, University of Münster and Max-Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
6 Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chuo, Chiba 260-8670, Japan
7 ReproCELL Inc., Chiyoda-ku, Tokyo 100-0011, Japan

CORRESPONDENCE Atsushi Iwama: aiwama{at}faculty.chiba-u.jp OR Hiromitsu Nakauchi: nakauchi{at}ims.u-tokyo.ac.jp

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.

Abbreviations used: AGM, aorta-gonad-mesonephros; CFC, colony-forming cell; EB, embryoid bodies; EPO, erythropoietin; EryP, primitive erythroid progenitor; ES, embryonic stem; HSC, hematopoietic stem cell; LTR, long-term repopulating; mSCF, mouse stem cell factor; SST-REX, signal sequence trap by retrovirus-mediated expression screening; TPO, thrombopoietin.


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