EPCR expression marks UM171-expanded CD34+ cord blood stem cells

被引：152

作者：

Fares, Iman ^{[1
]}

Chagraoui, Jalila ^{[1
]}

Lehnertz, Bernhard ^{[1
]}

MacRae, Tara ^{[1
]}

Mayotte, Nadine ^{[1
]}

Tomellini, Elisa ^{[1
]}

Aubert, Leo ^{[2
]}

Roux, Philippe P. ^{[2
,3
]}

Sauvageau, Guy ^{[1
,4
,5
]}

机构：

[1] Univ Montreal, Fac Med, Inst Res Immunol & Canc, Mol Genet Stem Cells Lab, Montreal, PQ, Canada

[2] Univ Montreal, Fac Med, Inst Res Immunol & Canc, Cell Signalling & Prote Res Unit, Montreal, PQ, Canada

[3] Univ Montreal, Dept Pathol & Cell Biol, Fac Med, Montreal, PQ, Canada

[4] Maisonneuve Rosemont Hosp, Div Hematol, Montreal, PQ, Canada

[5] Univ Montreal, Dept Med, Fac Med, Montreal, PQ, Canada

来源：

BLOOD | 2017年 / 129卷 / 25期

基金：

加拿大健康研究院;

关键词：

HUMAN HEMATOPOIETIC STEM; ACTIVATED PROTEIN-C; BONE-MARROW; MULTILINEAGE ENGRAFTMENT; ENDOTHELIAL-CELLS; EXPANSION; MICE; IDENTIFICATION; PROGENITORS; POPULATION;

D O I：

10.1182/blood-2016-11-750729

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

A small subset of human cord blood CD34(+) cells express endothelial protein C receptor (EPCR/CD201/PROCR) when exposed to the hematopoietic stem cell (HSC) self-renewal agonist UM171. In this article, we show that EPCR-positive UM171-treated cells, as opposed to EPCR-negative cells, exhibit robust multilineage repopulation and serial reconstitution ability in immunocompromised mice. In contrast to other stem cell markers, such as CD38, EPCR expression is maintained when cells are introduced in culture, irrespective of UM171 treatment. Although engineered overexpression of EPCR fails to reproduce the effects of UM171 on HSC activity, its expression is required for the repopulating activity of human HSCs. Altogether, our results indicate that EPCR is a reliable and cell culture-compatible marker of UM171-expanded human cord blood HSCs.

引用

页码：3344 / 3351

页数：8

共 29 条

[1] The ligand occupancy of endothelial protein C receptor switches the protease-activated receptor 1-dependent signaling specificity of thrombin from a permeability-enhancing to a banier-protective response in endothelial cells [J].

Bae, Jong-Sup ;

Yang, Likui ;

Manithody, Chandrashekhara ;

Rezaie, Alireza R. .

BLOOD, 2007, 110 (12) :3909-3916

[2] Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrow [J].

Balazs, AB ;

Fabian, AJ ;

Esmon, CT ;

Mulligan, RC .

BLOOD, 2006, 107 (06) :2317-2321

[3] Identification of stem cells in small intestine and colon by marker gene Lgr5 [J].

Barker, Nick ;

van Es, Johan H. ;

Kuipers, Jeroen ;

Kujala, Pekka ;

van den Born, Maaike ;

Cozijnsen, Miranda ;

Haegebarth, Andrea ;

Korving, Jeroen ;

Begthel, Harry ;

Peters, Peter J. ;

Clevers, Hans .

NATURE, 2007, 449 (7165) :1003-U1

[4] ISOLATION OF A CANDIDATE HUMAN HEMATOPOIETIC STEM-CELL POPULATION [J].

BAUM, CM ;

WEISSMAN, IL ;

TSUKAMOTO, AS ;

BUCKLE, AM ;

PEAULT, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (07) :2804-2808

[5] Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells [J].

Boitano, Anthony E. ;

Wang, Jian ;

Romeo, Russell ;

Bouchez, Laure C. ;

Parker, Albert E. ;

Sutton, Sue E. ;

Walker, John R. ;

Flaveny, Colin A. ;

Perdew, Gary H. ;

Denison, Michael S. ;

Schultz, Peter G. ;

Cooke, Michael P. .

SCIENCE, 2010, 329 (5997) :1345-1348

[6] Analysis of the clonal growth and differentiation dynamics of primitive barcoded human cord blood cells in NSG mice [J].

Cheung, Alice M. S. ;

Nguyen, Long V. ;

Carles, Annaick ;

Beer, Philip ;

Miller, Paul H. ;

Knapp, David J. H. F. ;

Dhillon, Kiran ;

Hirst, Martin ;

Eaves, Connie J. .

BLOOD, 2013, 122 (18) :3129-3137

[7] CDCP1 is a novel marker for hematopoietic stem cells [J].

Conze, T ;

Lammers, R ;

Kuçi, S ;

Scherl-Mostageer, M ;

Schweifer, N ;

Kanz, L ;

Bühring, HJ .

HEMATOPOIETIC STEM CELLS 2002: GENETICS AND FUNCTION, 2003, 996 :222-226

[8] Rapid Expansion of Human Hematopoietic Stem Cells by Automated Control of Inhibitory Feedback Signaling [J].

Csaszar, Elizabeth ;

Kirouac, Daniel C. ;

Yu, Mei ;

Wang, WeiJia ;

Qiao, Wenlian ;

Cooke, Michael P. ;

Boitano, Anthony E. ;

Ito, Caryn ;

Zandstra, Peter W. .

CELL STEM CELL, 2012, 10 (02) :218-229

[9] C1qRp defines a new human stem cell population with hernatopoietic and hepatic potential [J].

Danet, GH ;

Luongo, JL ;

Butler, G ;

Lu, MM ;

Tenner, AJ ;

Simon, MC ;

Bonnet, DA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (16) :10441-10445

[10]

Dorrell C, 2000, BLOOD, V95, P102

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