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Title: Membrane-anchored uPAR regulates the proliferation, marrow pool size, engraftment, and mobilization of mouse hematopoietic stem/progenitor cells
Authors: Tjwa, Marc
Sidenius, Nicolai
Moura, Rute Marisa Freire
Jansen, Alexandra
Theunissen, Koen
Andolfo, Annapaola
De Mol, Maria
Dewerchin, Mieke
Moons, Lieve
Blasi, Francesco
Verfaillie, Catherine
Carmeliet, Peter # ×
Issue Date: Apr-2009
Publisher: American Society for Clinical Investigation
Series Title: Journal of Clinical Investigation vol:119 issue:4 pages:1008-1018
Abstract: The mechanisms of BM hematopoietic stem/progenitor cell (HSPC) adhesion, engraftment, and mobilization remain incompletely identified. Here, using WT and transgenic mice, we have shown that membrane-anchored plasminogen activator, urokinase receptor ((M)uPAR) marks a subset of HSPCs and promotes the preservation of the size of this pool of cells in the BM. Loss or inhibition of (M)uPAR increased HSPC proliferation and impaired their homing, engraftment, and adhesion to the BM microenvironment. During mobilization, (M)uPAR was inactivated by plasmin via proteolytic cleavage. Cell-autonomous loss of the gene encoding (M)uPAR also impaired long-term engraftment and multilineage repopulation in primary and secondary recipient mice. These findings identify (M)uPAR and plasmin as regulators of the proliferation, marrow pool size, homing, engraftment, and mobilization of HSPCs and possibly also of HSCs.
URI: 
ISSN: 0021-9738
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory for Molecular Neurobiology
Molecular and Vascular Biology
Interdepartemental Stem Cell Institute (-)
Animal Physiology and Neurobiology Section - miscellaneous
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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