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Nat Cell Biol. 2017 Aug;19(8):891-903. doi: 10.1038/ncb3570. Epub 2017 Jul 17.

Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF.

Author information

1
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
2
Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
3
McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
4
Texas Scottish Rite Hospital for Children, 2222 Welborn Street, Dallas, Texas 75219, USA.
5
Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland.
6
Howard Hughes Medical Institute, USA.

Abstract

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 ∼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.

PMID:
28714970
PMCID:
PMC5536858
DOI:
10.1038/ncb3570
[Indexed for MEDLINE]
Free PMC Article

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