Journal of Clinical Investigation vol:119 issue:4 pages:1008-1018
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.