title: The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice.
abstract: Although recent advances have enabled hematopoietic stem cells (HSCs) to be enriched to near purity, more information about their characteristics will improve our understanding of their development and stage-related functions. Here, using microarray technology, we identified endothelial cell-selective adhesion molecule (ESAM) as a novel marker for murine HSCs in fetal liver. Esam was expressed at high levels within a Rag1(-) c-kit(Hi) Sca1(+) HSC-enriched fraction, but sharply down-regulated with activation of the Rag1 locus, a valid marker for the most primitive lymphoid progenitors in E14.5 liver. The HSC-enriched fraction could be subdivided into 2 on the basis of ESAM levels. Among endothelial antigens on hematopoietic progenitors, ESAM expression showed intimate correlation with HSC activity. The ESAM(Hi) population was highly enriched for multipotent myeloid-erythroid progenitors and primitive progenitors with lymphopoietic activity, and exclusively reconstituted long-term lymphohematopoiesis in lethally irradiated recipients. Tie2(+) c-kit(+) lymphohematopoietic cells in the E9.5-10.5 aorta-gonad-mesonephros region also expressed high levels of ESAM. Furthermore, ESAM was detected on primitive hematopoietic progenitors in adult bone marrow. Interestingly, ESAM expression in the HSC-enriched fraction was up-regulated in aged mice. We conclude that ESAM marks HSC in murine fetal liver and will facilitate studies of hematopoiesis throughout life.
authors.affiliation: Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Japan. yokotat@bldon.med.osaka-u.ac.jp
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yokota
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.forename: Stefan
authors.initials: S
authors.lastname: Butz
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.forename: Paul W
authors.initials: PW
authors.lastname: Kincade
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kanakura
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055879:Gene Knock-In Techniques; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000502:physiology; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; C428190:Esam protein, mouse