Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs
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 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.
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Macrophages regulate HSPCs indirectly through interaction with MSCs.
“Previous studies demonstrated that macrophages regulate HSPCs indirectly through interaction with MSCs.82”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [82]
Cites
Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., Shimizu, Y., Bronson, R. T., Gao, Y.-H., Inada, M., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80258-5 · Cited by 4,244 · see citing works
Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J. M., Behringer, R. R., & de Crombrugghe, B. (2002) · Cell · doi:10.1016/s0092-8674(01)00622-5 · Cited by 3,608 · see citing works
Osteoblastic cells regulate the haematopoietic stem cell niche
Calvi, L. M., Adams, G. B., Weibrecht, K. W., Weber, J. M., Olson, D. P., Knight, M. C., Martin, R. P., Schipani, E., Pajevic, P. D., Bringhurst, F. R., et al. (2003) · Nature · doi:10.1038/nature02040 · Cited by 3,433 · see citing works
Kiel, M. J., Yilmaz, Ö. H., Iwashita, T., Yilmaz, O. H., Terhorst, C., & Morrison, S. J. (2005) · Cell · doi:10.1016/j.cell.2005.05.026 · Cited by 3,168 · see citing works
Identification of the haematopoietic stem cell niche and control of the niche size
Zhang, J., Niu, C. S., Ye, L., Huang, H., He, X. C., Tong, W.-G., Ross, J., Haug, J., Johnson, T. J., Feng, J. Q., et al. (2003) · Nature · doi:10.1038/nature02041 · Cited by 2,948 · see citing works
Sugiyama, T., Kohara, H., Noda, M., & Nagasawa, T. (2006) · Immunity · doi:10.1016/j.immuni.2006.10.016 · Cited by 2,419 · see citing works
The relationship between the spleen colony-forming cell and the haemopoietic stem cell.
Schofield, R. (1978) · PubMed · Cited by 2,319 · see citing works
Tie2/Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche
Arai, F., Hirao, A., Ohmura, M., Sato, H., Matsuoka, S., Takubo, K., Ito, K., Koh, G. Y., & Suda, T. (2004) · Cell · doi:10.1016/j.cell.2004.07.004 · Cited by 1,958 · see citing works
van Rooijen, N., & Sanders, A. (1994) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)90012-4 · Cited by 1,763 · see citing works
Heissig, B., Hattori, K., Dias, S., Friedrich, M., Ferris, B., Hackett, N. R., Crystal, R. G., Besmer, P., Lyden, D. C., Moore, M. A. S., et al. (2002) · Cell · doi:10.1016/s0092-8674(02)00754-7 · Cited by 1,744 · see citing works
Signals from the Sympathetic Nervous System Regulate Hematopoietic Stem Cell Egress from Bone Marrow
Katayama, Y., Battista, M., Kao, W.-M., Hidalgo, A., Peired, A. J., Thomas, S. A., & Frenette, P. S. (2006) · Cell · doi:10.1016/j.cell.2005.10.041 · Cited by 1,412 · see citing works
Trophic macrophages in development and disease
Pollard, J. W. (2009) · Nature Reviews Immunology · doi:10.1038/nri2528 · Cited by 1,178 · see citing works
Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia
Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., et al. (2010) · Nature · doi:10.1038/nature08851 · Cited by 1,115 · see citing works
Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche
Celso, C. L., Fleming, H. E., Wu, J. W., Zhao, C. X., Miake-Lye, S., Fujisaki, J., Côté, D. C., Rowe, D. W., Lin, C. P., & Scadden, D. T. (2008) · Nature · doi:10.1038/nature07434 · Cited by 917 · see citing works
Hematopoiesis is severely altered in mice with an induced osteoblast deficiency
Višnjić, D., Kalajzić, Ž., Rowe, D. W., Katavić, V., Lorenzo, J., & Aguila, H. L. (2004) · Blood · doi:10.1182/blood-2003-11-4011 · Cited by 804 · see citing works
Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells
Kollet, Ó., Dar, A., Shivtiel, S., Kalinkovich, A., Lapid, K., Sztainberg, Y., Tesio, M., Samstein, R. M., Goichberg, P., Spiegel, A., et al. (2006) · Nature Medicine · doi:10.1038/nm1417 · Cited by 774 · see citing works
Lévesque, J.-P., Hendy, J., Takamatsu, Y., Simmons, P. J., & Bendall, L. J. (2003) · Journal of Clinical Investigation · doi:10.1172/jci15994 · Cited by 760 · see citing works
Self-citationChang, M. K., Raggatt, L. J., Alexander, K. A., Kuliwaba, J. S., Fazzalari, N. L., Schroder, K., Maylin, E. R., Ripoll, V. M., Hume, D. A., & Pettit, A. R. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.2.1232 · Cited by 696 · see citing works
Self-citationDetection of functional haematopoietic stem cell niche using real-time imaging
Xie, Y., Yin, T., Wiegraebe, W., He, X., Miller, D., Stark, D. A., Perko, K., Alexander, R. L., Schwartz, J. W., Grindley, J. C., et al. (2008) · Nature · doi:10.1038/nature07639 · Cited by 551 · see citing works
G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow
Semerad, C. L., Christopher, M. J., Liu, F., Short, B., Simmons, P. J., Winkler, I. G., Lévesque, J.-P., Chappel, J. C., Ross, F. P., & Link, D. C. (2005) · Blood · doi:10.1182/blood-2004-01-0272 · Cited by 500 · see citing works
Self-citationLévesque, J.-P., Takamatsu, Y., Nilsson, S. K., Haylock, D. N., & Simmons, P. J. (2001) · Blood · doi:10.1182/blood.v98.5.1289 · Cited by 486 · see citing works
Self-citationLévesque, J.-P., Hendy, J., Takamatsu, Y., Williams, B., Winkler, I. G., & Simmons, P. J. (2002) · Experimental Hematology · doi:10.1016/s0301-472x(02)00788-9 · Cited by 289 · see citing works
Self-citationLataillade, J., Clay, D., Bourin, P., Hérodin, F., Dupuy, C., Jasmin, C., & Bousse‐Kerdilès, M. L. (2002) · Blood · doi:10.1182/blood.v99.4.1117 · Cited by 277 · see citing works
Cytokines and hematopoietic stem cell mobilization
Nervi, B., Link, D. C., & DiPersio, J. F. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21043 · Cited by 257 · see citing works
Winkler, I. G., Barbier, V., Wadley, R. B., Zannettino, A. C. W., Williams, S., & Lévesque, J.-P. (2010) · Blood · doi:10.1182/blood-2009-07-233437 · Cited by 246 · see citing works
Self-citationCharacterization of hematopoietic progenitor mobilization in protease-deficient mice
Lévesque, J.-P., Liu, F., Simmons, P. J., Betsuyaku, T., Senior, R. M., Pham, C. T. N., & Link, D. C. (2004) · Blood · doi:10.1182/blood-2003-05-1589 · Cited by 240 · see citing works
Self-citationKöhler, A., Schmithorst, V. J., Filippi, M., Ryan, M. A., Daria, D., Gunzer, M., & Geiger, H. (2009) · Blood · doi:10.1182/blood-2008-12-195644 · Cited by 225 · see citing works
Expression and activity of osteoblast-targeted Cre recombinase transgenes in murine skeletal tissues
Liu, F., Woitge, H. W., Braut, A., Kronenberg, M. S., Lichtler, A. C., Mina, M., & Kream, B. E. (2004) · The International Journal of Developmental Biology · doi:10.1387/ijdb.041816fl · Cited by 195 · see citing works
Cooperation of β 2 ‐ and β 3 ‐adrenergic receptors in hematopoietic progenitor cell mobilization
Méndez‐Ferrer, S., Battista, M., & Frenette, P. S. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05390.x · Cited by 194 · see citing works
Lévesque, J.-P., Hendy, J., Winkler, I. G., Takamatsu, Y., & Simmons, P. J. (2003) · Experimental Hematology · doi:10.1016/s0301-472x(02)01028-7 · Cited by 187 · see citing works
Self-citationLévesque, J.-P., Winkler, I. G., Hendy, J., Williams, B., Helwani, F., Barbier, V., Nowlan, B., & Nilsson, S. K. (2007) · Stem Cells · doi:10.1634/stemcells.2006-0688 · Cited by 152 · see citing works
Self-citationLundberg, P., Allison, S. J., Lee, N. J., Baldock, P. A. J., Brouard, N., Rost, S., Enriquez, R. F., Sainsbury, A., Lamghari, M., Simmons, P. J., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609629200 · Cited by 143 · see citing works
Christopher, M. J., & Link, D. C. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.080612 · Cited by 127 · see citing works
Takamatsu, Y., Simmons, P. J., Moore, R. J., et al. (1998) · Blood · doi:10.1182/blood.v92.9.3465.421k35_3465_3473 · Cited by 124 · see citing works
Mundy, G. R., Yoneda, T., & Hiraga, T. (2001) · Seminars in Oncology · doi:10.1016/s0093-7754(01)90263-5 · Cited by 121 · see citing works
Three-dimensional model of bone marrow
Mohandas, N., & Prenant, M. (1978) · Blood · doi:10.1182/blood.v51.4.633.633 · Cited by 121 · see citing works
Foudi, A., Jarrier, P., Zhang, Y., et al. (2005) · Blood · doi:10.1182/blood-2005-02-0581 · Cited by 117 · see citing works
Grassinger, J., Haylock, D. N., Williams, B. P., et al. (2010) · Blood · doi:10.1182/blood-2009-12-260703 · Cited by 117 · see citing works
What is the true nature of the osteoblastic hematopoietic stem cell niche?
Askmyr, M., Sims, N. A., Martin, T. J., & Purton, L. E. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.03.004 · Cited by 99 · see citing works
Self-citationProspective Isolation of Mesenchymal Stem Cells from Mouse Compact Bone
Short, B., Brouard, N., & Simmons, P. J. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-060-7_16 · Cited by 86 · see citing works
Bryer, S. C., Fantuzzi, G., van Rooijen, N., & Koh, T. J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.2.1179 · Cited by 85 · see citing works
Verstegen, M. M. A., van Hennik, P. B., Terpstra, W. E., et al. (1998) · Blood · doi:10.1182/blood.v91.6.1966 · Cited by 77 · see citing works
Rehli, M., Sulzbacher, S., Pape, S., Ravasi, T., Wells, C. A., Heinz, S., Söllner, L., El Chartouni, C., Krause, S. W., Steingrimsson, E., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.11.7111 · Cited by 75 · see citing works
Sims, N. A., Brennan, K., Spaliviero, J. A., Handelsman, D. J., & Seibel, M. J. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00311.2005 · Cited by 74 · see citing works
Self-citationMobilization of hematopoietic stem cells: state of the art
Lévesque, J.-P., & Winkler, I. G. (2008) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e3282f42473 · Cited by 68 · see citing works
Self-citationDevelopment of Peritoneal Adhesions in Macrophage Depleted Mice
Burnett, S. H., Beus, B. J., Avdiushko, R., Qualls, J. E., Kaplan, A. M., & Cohen, D. A. (2005) · Journal of Surgical Research · doi:10.1016/j.jss.2005.08.026 · Cited by 67 · see citing works
Wu, A., Pettit, A. R., Toulson, S., Grøndahl, L., Mackie, E. J., & Cassady, A. I. (2008) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32238 · Cited by 31 · see citing works
Self-citationZoledronic Acid Inhibits Osteoclastogenesis in Vitro and in a Mouse Model of Inflammatory Osteolysis
Sudhoff, H. H., Faddis, B. T., Jung, J. Y., Hildmann, H., Ebmeyer, J., & Chole, R. A. (2003) · Annals of Otology Rhinology & Laryngology · doi:10.1177/000348940311200907 · Cited by 22 · see citing works
Three-dimensional model of bone marrow
Mohandas, N., & Prenant, M. (1978) · Blood · doi:10.1182/blood.v51.4.633.bloodjournal514633 · Cited by 20 · see citing works
Rao, M., Christopher, M. J., Woloszynek, J. R., et al. (2009) · Blood · doi:10.1182/blood.v114.22.563.563 · Cited by 3 · see citing works
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- Authors
- 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., & Lévesque, J.-P.
- Affiliations
- Mater Research (AU)
- The University of Melbourne (AU)
- The University of Queensland (AU)
- Department of Molecular Cell Biology, Vrije Universiteit, Amsterdam, The Netherlands; and
- Corresponding author
- Winkler, Ingrid G.
- Sims, Natalie A.
- Pettit, Allison R.
- Raggatt, Liza J.
- Lévesque, Jean-Pierre
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-12-02
- Volume
- 116
- Issue
- 23
- Pages
- 4815-4828
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2109525494
- Cited by
- 801
- References
- 50
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 40 · 2023: 39 · 2022: 39 · 2021: 68 · 2020: 70 · 2019: 61 · 2018: 58 · 2017: 67 · 2016: 49 · 2015: 60 · 2014: 64 · 2013: 45 · 2012: 60
- FWCI
- 29.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- hematopoietic stem cells, HSC niche, bone marrow-derived macrophages, endosteal niche, osteoblasts, G-CSF mobilization, hematopoietic stem cell mobilization, osteoblast activity, bone formation, HSC self-renewal, macrophage depletion, clodronate liposomes
- MeSH terms
- Animals, Bone Marrow Cells, Cell Differentiation, Cell Movement, Cell Separation, Flow Cytometry, Hematopoietic Stem Cells, Immunohistochemistry, Macrophages, Mice, Inbred C57BL, Granulocyte Colony-Stimulating Factor, Mice, Knockout, Cell Lineage, Reverse Transcriptase Polymerase Chain Reaction, Mice, Stem Cell Niche
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