Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs

Winkler, Ingrid G., Sims, Natalie A., Pettit, Allison R., Barbier, Valérie, Nowlan, Bianca, Helwani, Falak, Poulton, Ingrid J., van Rooijen, Nico van, Alexander, Kylie A., Raggatt, Liza J. and Levesque, Jean-Pierre (2010) Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood, 116 23: 4815-4828. doi:10.1182/blood-2009-11-253534


Author Winkler, Ingrid G.
Sims, Natalie A.
Pettit, Allison R.
Barbier, Valérie
Nowlan, Bianca
Helwani, Falak
Poulton, Ingrid J.
van Rooijen, Nico van
Alexander, Kylie A.
Raggatt, Liza J.
Levesque, Jean-Pierre
Title Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2010-12-02
Year available 2010
Sub-type Article (original research)
DOI 10.1182/blood-2009-11-253534
Open Access Status DOI
Volume 116
Issue 23
Start page 4815
End page 4828
Total pages 14
Place of publication Orlando, Fla., U.S.A.
Publisher Elsevier
Language eng
Abstract In the bone marrow, hematopoietic stem cells (HSCs) reside in specific niches near osteoblast-lineage cells at the endosteum. To investigate the regulation of these endosteal niches, we studied the mobilization of HSCs into the blood-stream in response to granulocyte colony-stimulating factor (G-CSF).We report that G-CSF mobilization rapidly depletes endosteal osteoblasts, leading to suppressed endosteal bone formation and decreased expression of factors required for HSC retention and self-renewal. Importantly, G-CSF administration also depleted a population of trophic endosteal macrophages (osteomacs) that support osteoblast function. Osteomac loss, osteoblast suppression, and HSC mobilization occurred concomitantly, suggesting that osteomac loss could disrupt endosteal niches. Indeed, in vivo depletion of macrophages, in either macrophage Fas-induced apoptosis (Mafia) transgenic mice or by administration of clodronate-loaded liposomes to wild-type mice, recapitulated the: (1) loss of endosteal osteoblasts and (2) marked reduction of HSC-trophic cytokines at the endosteum, with (3) HSC mobilization into the blood, as observed during G-CSF administration. Together, these results establish that bone marrow macrophages are pivotal to maintain the endosteal HSC niche and that the loss of such macrophages leads to the egress of HSCs into the blood. © 2010 by The American Society of Hematology.
Keyword Bone marrow
Stem cell
Macrophages
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 288701
Institutional Status UQ

 
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Created: Sun, 19 Dec 2010, 10:15:28 EST