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Bone marrow CD169(+) macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche
- Source :
- Europe PubMed Central, Journal of Experimental Medicine, Vol. 208, No 2 (2011) pp. 261-271, The Journal of Experimental Medicine, Journal of Experimental Medicine, 208(2), 261-271. Rockefeller University Press, Chow, A, Lucas, D, Hidalgo, A, Mendez-Ferrer, S, Hashimoto, D, Scheiermann, C, Battista, M, Leboeuf, M, Prophete, C, van Rooijen, N, Tanaka, M, Merad, M & Frenette, P S 2011, ' Bone marrow CD169(+) macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche ', Journal of Experimental Medicine, vol. 208, no. 2, pp. 261-271 . https://doi.org/10.1084/jem.20101688
- Publication Year :
- 2011
-
Abstract
- Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1hi monocytes (MOs), Gr-1lo MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169. Using MO and MΦ conditional depletion models, we found that reductions in BM mononuclear phagocytes led to reduced BM CXCL12 levels, the selective down-regulation of HSC retention genes in Nestin+ niche cells, and egress of HSCs/progenitors to the bloodstream. Furthermore, specific depletion of CD169+ MΦ, which spares BM MOs, was sufficient to induce HSC/progenitor egress. MΦ depletion also enhanced mobilization induced by a CXCR4 antagonist or granulocyte colony-stimulating factor. These results highlight two antagonistic, tightly balanced pathways that regulate maintenance of HSCs/progenitors in the niche during homeostasis, in which MΦ cross talk with the Nestin+ niche cell promotes retention, and in contrast, SNS signals enhance egress. Thus, strategies that target BM MΦ hold the potential to augment stem cell yields in patients that mobilize HSCs/progenitors poorly.
- Subjects :
- Male
Sialic Acid Binding Ig-like Lectin 1
Fluorescent Antibody Technique
Polymerase Chain Reaction
Monocytes
Mice
0302 clinical medicine
Monocytes/metabolism
Immunology and Allergy
Homeostasis
Receptors, Immunologic
Bone Marrow Cells/cytology/metabolism
Mice, Knockout
0303 health sciences
Membrane Glycoproteins
Receptor Cross-Talk/immunology
Membrane Glycoproteins/metabolism
Flow Cytometry
Hematopoietic Stem Cell Mobilization
Cell biology
Interleukin-10
Haematopoiesis
medicine.anatomical_structure
Homeostasis/immunology
Stem cell
Hematopoietic stem cell niche
Immunology
Receptors, Immunologic/metabolism
Bone Marrow Cells
Enzyme-Linked Immunosorbent Assay
Biology
Article
Colony-Forming Units Assay
03 medical and health sciences
Macrophages/metabolism
medicine
Chemokine CXCL12/metabolism
Animals
Progenitor cell
Mesenchymal Stromal Cells/cytology
030304 developmental biology
DNA Primers
Interleukin-10/genetics
DNA Primers/genetics
Hematopoietic Stem Cells/cytology
Macrophages
Mesenchymal stem cell
Mesenchymal Stem Cells
Receptor Cross-Talk
Nestin
Hematopoietic Stem Cells
Molecular biology
Chemokine CXCL12
Mice, Inbred C57BL
Bone marrow
030215 immunology
Subjects
Details
- ISSN :
- 00221007
- Volume :
- 208
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....5299f89d89a892c4371ffd3864e816d0