title: Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin.
abstract: Little is known about hematopoietic stem cell (HSC) development from mesoderm. To gain more information on the intraembryonic HSC site of origin, we purified multipotent hematopoietic progenitors from the aorta-gonads-mesonephros (AGM) of mice. This population, expressing c-Kit, AA4.1, CD31, and CD41, but not Flk1, and mainly negative for CD45, proved capable of long-term reconstitution in sublethally irradiated Rag2gammac(-/-) recipients. We assigned the expression of GATA-2, GATA-3, and lmo2 to AGM-HSC, whereas erythromyeloid progenitors express only GATA-2. This unique combination of surface markers and transcription factors could be allocated in the AGM to the intraaortic clusters and the subaortic patches underlying aortic endothelial cells. Taken together, those data indicate that embryonic HSCs (i) differ from their fetal liver and adult counterpart by the low expression of CD45, (ii) do not colocalize with aortic endothelial cells as previously thought, and (iii) are localized, at 10.5 days postcoitum, in the splanchnic mesoderm underlying aortic endothelial cells, within GATA-3(+)CD31(+) cell clusters.
authors.affiliation: Unité du Développement des Lymphocytes, Unité de Recherche Associée Centre National de la Recherche Scientifique 1961, Institut Pasteur, 25 Rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Julien Y
authors.initials: JY
authors.lastname: Bertrand
authors.forename: Sébastien
authors.initials: S
authors.lastname: Giroux
authors.forename: Rachel
authors.initials: R
authors.lastname: Golub
authors.forename: Michèle
authors.initials: M
authors.lastname: Klaine
authors.forename: Abdelali
authors.initials: A
authors.lastname: Jalil
authors.forename: Laurent
authors.initials: L
authors.lastname: Boucontet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Godin
authors.forename: Ana
authors.initials: A
authors.lastname: Cumano
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers; D019070:Cell Lineage; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D006066:Gonads / Q000166:cytology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008648:Mesoderm / Q000166:cytology*; D008650:Mesonephros / Q000166:cytology / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL
chemical_list: D015415:Biomarkers; D017493:Leukocyte Common Antigens