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 Kitl gene from adipocytes and bone marrow stroma cells using Adipoq-Cre and Osx1-Cre, respectively. We found that both Adipoq-Kitl knockout (KO) and Osx1-Kitl 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 progen ito r cells in th e bone marrow dynamically responded to metabolic challenges including high fat diet, â3-adrenergic activation, thermoneutrality, and aging. However, such responses, particularly within the myeloid compartment, were largely impaired in Adipoq-Kitl 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.
Bibliographical noteFunding Information:
This work was supported by National Key R&D Program of China (2017YFD0500505), Fundamental Research Funds for the Central Universities (KJQN201604), National Natural and Science Foundation of China (31500944), Natural Science Foundation of Jiangsu Province (BK20150687), and China Scholarship Council postdoctoral fellowship (201606855010) to ZH; Natural Science Foundation of Jiangsu Province (BK20170147) to ZZ; National Natural and Science Foundation of China (81770543), American Diabetes Association (18-IBS-167), and NIAID (R01AId139420 and R21AI140109) to H-BR.