In this WP, we investigate the differentiation trajectories of cellular subpopulations in human and mouse adipose tissue, as well as the intrinsic and extrinsic molecular signals driving the specification of these subpopulations. We are particularly interested in the transcriptional regulation of adipocyte the differentiation from early stromal progenitors to preadipocytes and mature adipocytes. Using spatial single cell analyses, we investigate adipose tissue architecture and identify niche-dependent signals driving cellular plasticity and differentiation. Furthermore, using our unique human cohorts we investigate how adipose tissue plasticity is affected by weight gain and weight loss.