Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

By O. Naveiras, V. Nardi, P. Wenzel, F. Fahey, G. Daley. Nature, 2009

1,064 citations recorded by the source corpus.

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-γ 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.

Subfields: Emergency Medicine, Genetics, Hematology

View Paper: https://www.semanticscholar.org/paper/d05519128385929e5a8c4ba9b74899ece5782427

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Jay J Cao
2. Aviv Bergman
3. V. Horsley
4. B. Spiegelman
5. P. Frenette
6. Robert D. Leclerc

In Hematology

1. Sandra Pinho
2. P. Frenette

Citations in the corpus

• Impact of Obesity and Metabolic Syndrome on Immunity. (2016, background): “As such, adipocytes in bone marrow have been shown to suppress hematopoiesis (45).”
• The elusive nature and function of mesenchymal stem cells (2011, positive): “The BM stroma is also composed of MSC-derived adipocytes, which function as negative regulators of early haematopoietic progenitors through unknown molecular mechanism”
• Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration (2017, background): “Nevertheless, marrow adipogenesis is associated with impaired hematopoiesis (Naveiras et al., 2009).”
• Arteriolar niches maintain haematopoietic stem cell quiescence (2013, positive): “Unlike long bones which are mostly occupied by adipocytes in adult humans 29 , the sternum exhibits rich hematopoietic activity in both species.”
• Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling (2011, background): “Hematopoietic stem cell engraftment is inhibited by mature adipocytes within bone marrow (Naveiras et al., 2009).”
• Effects of obesity on bone metabolism (2011, background): “Bone marrow adipocytes also may directly regulate the osteoclast progenitors, hematopoietic cells [ 80 ].”
• What We Talk About When We Talk About Fat (2014, positive): “There is an inverse relationship between the number of fat cells and the number of hematopoietic precursors, and elimination of marrow fat by genetic or pharmacologic means enhances the rate of engraftment following radioablation (Naveiras et al., 2009).”