Journal
NATURE CELL BIOLOGY
Volume 19, Issue 8, Pages 891-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3570
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Funding
- Leukemia and Lymphoma Society
- Thousand Talents Plan-Youth in China
- National Institute on Aging [R37 AG024945]
- Cancer Prevention and Research Institute of Texas
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Endothelial cells and leptin receptor(+) (LepR(+)) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including stem cell factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER+ progenitors, which represent similar to 5% of LepR(+) cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited haematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival. Scf from LepR(+) cells, but not endothelial, haematopoietic or osteoblastic cells, also promoted regeneration. In non-irradiated mice, Scf deletion using Adipoq-Cre/ER did not affect HSC frequency in long bones, which have few adipocytes, but depleted HSCs in tail vertebrae, which have abundant adipocytes. A-ZIP/F1 'fatless' mice exhibited delayed haematopoietic regeneration in long bones but not in tail vertebrae, where adipocytes inhibited vascularization. Adipocytes are a niche component that promotes haematopoietic regeneration.
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