Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN, USA.
Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agriculture University, Nanjing, Jiangsu, China.
Haematologica. 2019 Sep;104(9):1731-1743. doi: 10.3324/haematol.2018.205856. Epub 2019 Feb 21.
Hematopoiesis is dynamically regulated by metabolic cues in homeostatic and stressed conditions; however, the cellular and molecular mechanisms mediating the metabolic sensing and regulation remain largely obscure. Bone marrow adipose tissue remodels in various metabolic conditions and has been recently proposed as a niche for hematopoietic stem cells after irradiation. Here, we investigated the role of marrow adipose tissue-derived hematopoietic cytokine stem cell factor in unperturbed hematopoiesis by selectively ablating the gene from adipocytes and bone marrow stroma cells using and , respectively. We found that both knockout (KO) and KO mice diminished hematopoietic stem and progenitor cells and myeloid progenitors in the bone marrow and developed macrocytic anemia at the steady-state. The composition and differentiation of hematopoietic progenitor cells in the bone marrow dynamically responded to metabolic challenges including high fat diet, β3-adrenergic activation, thermoneutrality, and aging. However, such responses, particularly within the myeloid compartment, were largely impaired in KO mice. Our data demonstrate that marrow adipose tissue provides stem cell factor essentially for hematopoiesis both at the steady state and upon metabolic stresses.
造血是由稳态和应激条件下的代谢线索动态调节的；然而，介导代谢感应和调节的细胞和分子机制在很大程度上仍不清楚。骨髓脂肪组织在各种代谢条件下进行重塑，并且最近被提议作为照射后造血干细胞的龛位。在这里，我们使用 和 分别从脂肪细胞和骨髓基质细胞中选择性地敲除 基因，研究了骨髓脂肪组织来源的造血细胞因子干细胞因子在未受干扰的造血中的作用。我们发现， 和 基因敲除 (KO) 小鼠均减少了骨髓中的造血干细胞和祖细胞，并在稳态时发展为巨红细胞性贫血。骨髓中造血祖细胞的组成和分化对代谢挑战（包括高脂肪饮食、β3-肾上腺素能激活、热中性和衰老）做出动态响应。然而，在 基因敲除小鼠中，这些反应，特别是在髓系中，受到了很大的损害。我们的数据表明，骨髓脂肪组织为造血提供了干细胞因子，这在稳态和代谢应激下都是必不可少的。
