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Stem Cells Dev. 2019 Jan 14. doi: 10.1089/scd.2018.0154. [Epub ahead of print]

Vascular Endothelial Cadherin and Angiotensin-Converting Enzyme Co-Expression Marks Highly Proliferative Hematopoietic Stem Cells in Human Embryonic Liver.

Author information

1
1 Inserm, UMR 1170, Villejuif, France.
2
2 Paris-Saclay University, Villejuif, France.
3
3 Gustave Roussy, Villejuif, France.
4
4 Inserm UMS 33, Villejuif, France.
5
5 André Lwoff Institute (IFR89), Villejuif, France.
6
6 Paris-Saclay University, Villejuif, France.
7
7 Inserm UMR 935, Villejuif, France.
8
8 Obstetrics and Gynecology Department, René-Dubos Hospital, Pontoise, France.

Abstract

Despite advances to engineer transplantable hematopoietic stem and progenitor cells (HSPCs) for research and therapy, an in-depth characterization of the developing human hematopoietic system is still lacking. The human embryonic liver is at the crossroad of several hematopoietic sites and harbors a complex hematopoietic hierarchy, including the first actively dividing HSPCs that will further seed the definitive hematopoietic organs. However, few are known about the phenotypic and functional HSPC organization operating at these stages of development. In this study, using a combination of four endothelial and hematopoietic surface markers, that is, the endothelial-specific marker Vascular endothelial-cadherin (Cdh5, CD144), the pan-leukocyte antigen CD45, the hemato-endothelial marker CD34, and the Angiotensin-converting enzyme (ACE, CD143), we identified distinct HSPC subsets, and among them, a population co-expressing the four markers that uniquely harbored an outstanding proliferation potential both ex vivo and in vivo. Moreover, we traced back this population to the yolk sac (YS) and aorta-gonad-mesonephros (AGM) sites of hematopoietic emergence. Taken together, our data will help to identify human HSPC self-renewal and amplification mechanisms for future cell therapies.

KEYWORDS:

VE-cadherin; angiotensin-converting enzyme; embryonic liver; hematopoietic stem and progenitor cell; human embryo

PMID:
30426841
DOI:
10.1089/scd.2018.0154

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