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.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Ivanovs A,Rybtsov S,Anderson RA,Turner ML,Medvinsky A

doi

10.1016/j.stemcr.2014.02.004

subject

Has Abstract

pub_date

2014-03-27 00:00:00

pages

449-56

issue

4

issn

2213-6711

pii

S2213-6711(14)00056-3

journal_volume

2

pub_type

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