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Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells.

Authors :
Butler JM
Nolan DJ
Vertes EL
Varnum-Finney B
Kobayashi H
Hooper AT
Seandel M
Shido K
White IA
Kobayashi M
Witte L
May C
Shawber C
Kimura Y
Kitajewski J
Rosenwaks Z
Bernstein ID
Rafii S
Source :
Cell stem cell [Cell Stem Cell] 2010 Mar 05; Vol. 6 (3), pp. 251-64.
Publication Year :
2010

Abstract

Bone marrow endothelial cells (ECs) are essential for reconstitution of hematopoiesis, but their role in self-renewal of long-term hematopoietic stem cells (LT-HSCs) is unknown. We have developed angiogenic models to demonstrate that EC-derived angiocrine growth factors support in vitro self-renewal and in vivo repopulation of authentic LT-HSCs. In serum/cytokine-free cocultures, ECs, through direct cellular contact, stimulated incremental expansion of repopulating CD34(-)Flt3(-)cKit(+)Lineage(-)Sca1(+) LT-HSCs, which retained their self-renewal ability, as determined by single-cell and serial transplantation assays. Angiocrine expression of Notch ligands by ECs promoted proliferation and prevented exhaustion of LT-HSCs derived from wild-type, but not Notch1/Notch2-deficient, mice. In transgenic notch-reporter (TNR.Gfp) mice, regenerating TNR.Gfp(+) LT-HSCs were detected in cellular contact with sinusoidal ECs. Interference with angiocrine, but not perfusion, function of SECs impaired repopulation of TNR.Gfp(+) LT-HSCs. ECs establish an instructive vascular niche for clinical-scale expansion of LT-HSCs and a cellular platform to identify stem cell-active trophogens.<br /> (2010 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1875-9777
Volume :
6
Issue :
3
Database :
MEDLINE
Journal :
Cell stem cell
Publication Type :
Academic Journal
Accession number :
20207228
Full Text :
https://doi.org/10.1016/j.stem.2010.02.001