CXCL12 and obesity due to melanocortin 4 receptor deficiency: Several studies in mice report that high-fat diet (HFD) and/or diet-induced obesity cause loss of HSC quiescence and induce differentiation, resulting in a shift from self-renewing HSCs toward mature progenitors.62–64 HFD has been reported to create a myeloid bias in mice and to decrease expression of CXCL12 and Jagged-1.64 Similarly, obese humans have higher numbers of granulocytes and monocytes in peripheral blood consistent with increased myelopoiesis.65 Whether the decrease in CXCL12 and Jagged-1 can explain the loss of stemness of HSCs during obesity is a subject for further research.