Identification of the niche and phenotype of the first human hematopoietic stem cells

Andrejs Ivanovs, Stanislav Rybtsov, Richard A Anderson, Marc L Turner, Alexander Medvinsky

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)449-56
Number of pages8
JournalStem Cell Reports
Volume2
Issue number4
Early online date27 Mar 2014
DOIs
Publication statusPublished - 8 Apr 2014

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