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Editorials
Figure 1. Bone marrow adipocytes influence the maintenance of hematopoietic stem cell (HSC) and hematopoiesis. Bone marrow cellularity is complex, but is main- ly composed of hematopoietic cells and bone marrow adipocytes (BMA), which appear after birth and accumulate with age, obesity and irradiation. BMA originate from osterix-positive (+) progenitor cells and secret adiponectin, stem cell factor (SCF) and other functional factors. In this study, Zhang et al.5 have demonstrated that BMAT-derived SCF plays important roles in HSC maintenance and hematopoietic differentiation under baseline, aging and obese conditions. Deficiency of SCF in BMAT hinders the self-renewal of HSC by influencing the bone marrow microenvironment and hematopoiesis through unknown mechanisms. RBC: red blood cell; MPP: multipotent progenitor; CMP: common myeloid progenitor; MEP: megakaryocyte-erythrocyte progenitor; GMP: granulocyte-monocyte progenitor; CLP: common lymphoid progenitor.
diet (HFD)-induced obesity. Whereas HFD, per se, did not increase the SCF concentrations in bone marrow super- natant, this treatment increased bone marrow cellularity, HSPC, and mature blood cells, including granulocytes, monocytes and lymphocytes, the effects of which were eliminated by SCF deficiency in adipocytes. Aging causes similar increases in the HSPC, especially in the myeloid lineage populations, and most of these effects required adipocyte-derived SCF. Further, these investigators explored a potential role for SCF in mediating effects of a β3-adrenergic receptor agonist. Activation of these recep- tors induces the lipolysis of white adipocytes, and while although BMAT lipolysis is relatively resistant to β-adren- ergic signaling,14 Zhang et al. observed that after adminis- tration of a β3-adrenoceptor agonist, CL316, 243, SCF expression was increased in bone marrow without signif- icant changes in the BMA numbers.5 Consistent with the elevated SCF in bone marrow, the numbers of HSPC, including Lin-Sca1+c-Kit+ (LSK) cell, multipotent progeni- tor (MPP), MEP, GMP and CLP were increased by CL316, 243 injection, the effects of which were compromised by adipocyte-specific deficiency of SCF. Based on the animal
models described above, it should be noted that alter- ations of BMAT, SCF and hematopoiesis were not tightly associated under these conditions, which suggests that hematopoietic metabolism is regulated by factors beyond BMAT and its derived SCF. The global effects of obesity, aging and β3-adrenoceptor activation cannot be excluded from this scenario. In addition, other secreted factors from BMAT may also play significant roles in hematopoiesis under these conditions. Unfortunately, the secretome of BMAT remains largely unexplored.
In summary, Zhang et al.5 have extended our under- standing of the roles of BMAT in the bone marrow niche and the interaction between BMA and hematopoietic cells. They thoroughly addressed their hypotheses using a variety of animal models and complete profiling of hematopoietic changes. However, due to the complexity of whole-body metabolism and the lack of BMA-specific transgenic tools, further work will be required to deter- mine whether BMA-derived SCF regulates hematopoiesis directly through Kitl/c-Kit signaling in hematopoietic cells or indirectly by changing the microenvironment of the bone marrow niche.
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haematologica | 2019; 104(9)