VE-Cadherin and ACE Co-Expression Marks Highly Proliferative Hematopoietic Stem Cells in Human Embryonic Liver

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...

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Bibliographic Details
Published in:	Stem cells and development Vol. 28; no. 3; p. 165
Main Authors:	Zhang, Yanyan, Clay, Denis, Mitjavila-Garcia, Maria Teresa, Alama, Aurélie, Mennesson, Benoit, Berseneff, Helene, Louache, Fawzia, Bennaceur-Griscelli, Annelise, Oberlin, Estelle
Format:	Journal Article
Language:	English
Published:	United States 01-02-2019
Subjects:	Antigens, CD - genetics Antigens, CD - metabolism Cadherins - genetics Cadherins - metabolism Cell Differentiation Cell Lineage Cell Proliferation Cells, Cultured Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Hematopoietic Stem Cells - physiology Human Embryonic Stem Cells - cytology Human Embryonic Stem Cells - metabolism Human Embryonic Stem Cells - physiology Humans Liver - cytology Liver - embryology Peptidyl-Dipeptidase A - genetics Peptidyl-Dipeptidase A - metabolism hematopoietic stem and progenitor cell human embryo embryonic liver VE-cadherin angiotensin-converting enzyme
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Summary:	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.
ISSN:	1557-8534
DOI:	10.1089/scd.2018.0154