title: Identification of the niche and phenotype of the first human hematopoietic stem cells.
abstract: In various vertebrate species, the dorsal aorta (Ao) is the site of specification of adult hematopoietic stem cells (HSCs). It has been observed that the upregulation of essential hematopoietic transcription factors and the formation of specific intra-aortic hematopoietic cell clusters occur predominantly in the ventral domain of the Ao (AoV). In the mouse, the first HSCs emerge in the AoV. Here, we demonstrate that in the human embryo the first definitive HSCs also emerge asymmetrically and are localized to the AoV, which thus identifies a functional niche for developing human HSCs. Using magnetic cell separation and xenotransplantations, we show that the first human HSCs are CD34(+)VE-cadherin(+)CD45(+)C-KIT(+)THY-1(+)Endoglin(+)RUNX1(+)CD38(-/lo)CD45RA(-). This population harbors practically all committed hematopoietic progenitors and is underrepresented in the dorsal domain of the Ao (AoD) and urogenital ridges (UGRs). The present study provides a foundation for analysis of molecular mechanisms underpinning embryonic specification of human HSCs.
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, Scotland, UK.
authors.forename: Andrejs
authors.initials: A
authors.lastname: Ivanovs
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, Scotland, UK.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Rybtsov
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, Scotland, UK ; Scottish National Blood Transfusion Service, Edinburgh EH17 7QT, Scotland, UK.
authors.forename: Marc L
authors.initials: ML
authors.lastname: Turner
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, Scotland, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Medvinsky
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D010641:Phenotype; D055153:Stem Cell Niche
chemical_list: D000954:Antigens, Surface
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