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

BO Zhou, H Yu, R Yue, Z Zhao, JJ Rios, O Naveiras… - Nature cell …, 2017 - nature.com
BO Zhou, H Yu, R Yue, Z Zhao, JJ Rios, O Naveiras, SJ Morrison
Nature cell biology, 2017nature.com
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 …
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.
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