White adipocytes serve as an energy reservoir to store excessive calories in the form of lipid droplets and protect other tissues or organs from ectopic lipid accumulation. Brown adipocytes express uncoupling protein 1 and are integral to adaptive thermogenesis. Whereas the functions of adipocytes in either white or brown adipose tissues are well documented, our knowledge of bone marrow adipocytes (BMA) remains in its infancy. Bone marrow adipose tissue (BMAT) occupies approximately 50-70% of the bone marrow volume in human adults. 1 It is a dynamic tissue and responds to multiple metabolic conditions. For example, BMAT increases with obesity, aging, diabetes, caloric restriction, and irradiation. 2 Although the significance of BMAT expansion under these conditions is still largely unknown, BMA interact locally with hematopoietic and bone cells, and contribute to global metabolism through secretion of adiponectin, leptin, stem cell factor (SCF), and other functional factors. For example, A-ZIP/F1 mice, which lack adipose tissues throughout the body, including BMAT, have delayed hematopoietic regeneration in long bones after irradiation. 3 Our latest work also observed that depletion of BMA by bariatric surgery is associated with a decrease in bone marrow erythroid cells and anemia. 4 The importance of BMA and the derived factors on hematopoiesis is further enhanced by a study in this issue of the Journal, in which Zhang et al. 5 demonstrate that BMAT-derived SCF mediates metabolic regulation of hematopoiesis.

Stem cell factor, also known as Kit ligand (Kitl), is a hematopoietic cytokine expressed in fibroblasts and endothelial cells, as well as in BMA. 3 Together with its receptor, c-Kit, SCF plays important roles in the maintenance of hematopoietic stem cells (HSC) and hematopoiesis. Blockade of the interaction between c-Kit and SCF with antic-Kit antibody promotes the clearance of HSC, which indicates the importance of Kitl/c-Kit signaling in HSC selfrenewal. 6 Loss-of-function mutations in c-Kit cause macrocytic anemia, or even embryonic lethality under some severe mutations. 7 Inversely, mice with c-Kit gain-of-function mutations developed erythrocytosis compatible with myeloproliferative disorders. 8 Analyses of multiple cell populations isolated from bone marrow and adipose tissue have demonstrated that BMA and LepR-positive (+) stromal cells are the primary sources of SCF, which is required for the regeneration of HSC and hematopoiesis after irradiation. 3 Zhang et al. report that BMA-derived SCF is important for hematopoietic homeostasis under basal (Figure 1), obese and aging conditions, and in response to ß3-adrenergic agonists. 5 Knockout of SCF in adipocytes with an adiponectin driver does not influence circulating SCF concentrations or phenotypes of the peripheral adipose depots, which is perhaps due to compensatory expression of SCF from other sources, such as endothelial cells, fibroblasts and stromal cells. Interestingly, Zhang et al. observed a significant loss of SCF