Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs
| Autor: | Kylie A. Alexander, Nico van Rooijen, Bianca Nowlan, Jean-Pierre Levesque, Natalie A. Sims, Ingrid G. Winkler, Ingrid J. Poulton, Falak Helwani, Liza J. Raggatt, Valerie Barbier, Allison R. Pettit |
|---|---|
| Přispěvatelé: | Molecular cell biology and Immunology, CCA - Immuno-pathogenesis |
| Rok vydání: | 2010 |
| Předmět: |
Hematopoietic stem cell niche
Immunology Population Bone Marrow Cells Cell Separation Biology Biochemistry Mice Cell Movement Granulocyte Colony-Stimulating Factor medicine Animals Cell Lineage Stem Cell Niche education Mice Knockout Endosteum education.field_of_study Reverse Transcriptase Polymerase Chain Reaction Macrophages Hematopoietic stem cell Cell Differentiation Osteoblast Cell Biology Hematology Flow Cytometry Hematopoietic Stem Cells Immunohistochemistry Cell biology Mice Inbred C57BL Haematopoiesis medicine.anatomical_structure Bone marrow Stem cell |
| Zdroj: | Winkler, I G, Sims, N A, Pettit, A R, Barbier, V, Nowlan, B, Helwani, F, Poulton, I J, van Rooijen, N, Alexander, K A, Raggatt, L J & Levesque, J P 2010, ' Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs ', Blood, vol. 116, no. 23, pp. 4815-4828 . https://doi.org/10.1182/blood-2009-11-253534 Blood, 116(23), 4815-4828. American Society of Hematology |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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 bloodstream 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|