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

Bo O. Zhou, Hua Yu, Rui Yue, Zhiyu Zhao, Jonathan J. Rios, Olaia Naveiras, Sean J. Morrison

Research output: Contribution to journalArticle

118 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)891-903
Number of pages13
JournalNature Cell Biology
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2017

ASJC Scopus subject areas

  • Cell Biology

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