title: Membrane-anchored uPAR regulates the proliferation, marrow pool size, engraftment, and mobilization of mouse hematopoietic stem/progenitor cells.
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 (MuPAR) marks a subset of HSPCs and promotes the preservation of the size of this pool of cells in the BM. Loss or inhibition of MuPAR increased HSPC proliferation and impaired their homing, engraftment, and adhesion to the BM microenvironment. During mobilization, MuPAR was inactivated by plasmin via proteolytic cleavage. Cell-autonomous loss of the gene encoding MuPAR also impaired long-term engraftment and multilineage repopulation in primary and secondary recipient mice. These findings identify MuPAR and plasmin as regulators of the proliferation, marrow pool size, homing, engraftment, and mobilization of HSPCs and possibly also of HSCs.
authors.affiliation: VIB--Vesalius Research Center, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Tjwa
authors.forename: Nicolai
authors.initials: N
authors.lastname: Sidenius
authors.forename: Rute
authors.initials: R
authors.lastname: Moura
authors.forename: Sandra
authors.initials: S
authors.lastname: Jansen
authors.forename: Koen
authors.initials: K
authors.lastname: Theunissen
authors.forename: Annapaola
authors.initials: A
authors.lastname: Andolfo
authors.forename: Maria
authors.initials: M
authors.lastname: De Mol
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.forename: Catherine
authors.initials: C
authors.lastname: Verfaillie
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D006085:Graft Survival; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010958:Plasminogen / Q000172:deficiency / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C524899:Plaur protein, mouse; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen