Cited by 1,129Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchAdipose Tissue and Metabolism

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Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment

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Naveiras, Olaia, Nardi, Valentina, Wenzel, Pamela L., Hauschka, Peter V., Fahey, Frederic, Daley, George Q.·2009·Nature

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Abstract

Osteoblasts and endothelium constitute functional niches that support haematopoietic stem cells in mammalian bone marrow. Adult bone marrow also contains adipocytes, the number of which correlates inversely with the haematopoietic activity of the marrow. Fatty infiltration of haematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia. To explore whether adipocytes influence haematopoiesis or simply fill marrow space, we compared the haematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. Here we show, by flow cytometry, colony-forming activity and competitive repopulation assay, that haematopoietic stem cells and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 'fatless' mice, which are genetically incapable of forming adipocytes, and in mice treated with the peroxisome proliferator-activated receptor-gamma inhibitor bisphenol A diglycidyl ether, which inhibits adipogenesis, marrow engraftment after irradiation is accelerated relative to wild-type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone-marrow microenvironment, and indicate that antagonizing marrow adipogenesis may enhance haematopoietic recovery in clinical bone-marrow transplantation.

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Authors: Naveiras, O., Nardi, V., Wenzel, P. L., Hauschka, P. V., Fahey, F., & Daley, G. Q.
Affiliations: Brigham and Women's Hospital (US)
Harvard University (US)
Boston Children's Hospital (US)
Corresponding author: Daley, George Q.
ORCID: Naveiras, Olaia
Nardi, Valentina
Wenzel, Pamela L.
Fahey, Frederic
Daley, George Q.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2009-06-10
Volume: 460
Issue: 7252
Pages: 259-263
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature08099
PMC: PMC2831539
OpenAlex: W2100140007
Cited by: 1,129
References: 31
Citations by year: 2026: 22 · 2025: 49 · 2024: 64 · 2023: 68 · 2022: 62 · 2021: 84 · 2020: 96 · 2019: 71 · 2018: 71 · 2017: 94 · 2016: 69 · 2015: 65 · 2014: 59 · 2013: 69 · 2012: 67
FWCI: 39.67
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders: Howard Hughes Medical Institute
National Institutes of Health (DP1OD000256)
National Heart, Lung, and Blood Institute (T32HL007623)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK059279, R01DK070055)
Topics: Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: bone marrow adipocytes, hematopoiesis, hematopoietic stem cells, hematopoietic progenitor cells, adipogenesis, bone marrow transplantation, hematopoietic recovery, DGEBA, PPARγ
MeSH terms: Bisphenol A Compounds, Animals, Benzhydryl Compounds, Bone Marrow Cells, Cell Line, Epoxy Compounds, Femur, Hematopoiesis, Hematopoietic Stem Cells, Homeostasis, Mice, Inbred C57BL, Osteogenesis, Spine, Tail, Thorax, Tibia, Bone Marrow Transplantation, Stromal Cells, Adipocytes, Adiposity, Adipogenesis, Mice

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Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment

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