Interplay between resident tissue macrophages and adipocyte stem cells to control fat growth – MacFAT

Adipocyte stem cells (ASC) are key regulators of adipose tissue growth in obesity and the consortium recently uncovered a crucial role of adipose tissue resident macrophages in regulating ASC fate and functions. The first aim of our research proposal is to prove and decode using unique in vivo models the interplay between a specific subset of adipose tissue macrophage and ASC. These preclinical observations will be confirmed in human fat by exploring in depth the metabolic cross-talk between adipose tissue resident macrophages and ASC at the spatial and single-cell levels using cutting-edge technologies in lean and obese patients. This will enable the generation of a comprehensive multi-dimensional omics cell atlas of human adipose tissue in health and disease. Strong of their complementary expertise, our consortium will also build human adipose tissue organoid derived from obese patient induced pluripotent stem cells (iPSC) containing macrophages to further model and decipher metabolic and adipogenic processes. In addition, new metabolic tracing capabilities will be developed to identify at the molecular level the origin and fate of metabolites and their contribution in adipose tissue growth (adipogenesis). Such macrophage-sufficient adipose tissue organoid platform will allow to validate mechanisms inferred from our multi-omics cell atlas and to test potential interventions.