Adipose tissues are localized in multiple regions of the body, where they control different physiological mechanisms through different specialized adipocyte subtypes. How these different adipocytes types develop and are maintained is not known. Using new technologies for propagation of multipotent mesenchymal progenitor cells from human adipose tissue, in combination with single-cell and single nuclei transcriptomics, we have identified signaling pathways mediating the determination and differentiation of these cells towards multiple adipocyte subtypes. We have also used these cells to generate hybrid human/mouse adipose tissues i-vivo, and define the mechanisms by which adipocytes recruit the vascular and neural structures necessary for their specialized functions. In particular, we have defined mechanisms elicited by human UCP-1 expressing adipocytes to maintain their thermogenic function, which involve modulation of the catecholamine degrading enzyme MAOA. How these findings might be leveraged to develop new metabolic therapies will be discussed.