A stromal cell population that inhibits adipogenesis in mammalian fat depots

Adipocyte development and differentiation have an important role in the aetiology of obesity and its co-morbidities^1,2. Although multiple studies have investigated the adipogenic stem and precursor cells that give rise to mature adipocytes^3-14, our understanding of their in vivo origin and properties is incomplete^2,15,16. This is partially due to the highly heterogeneous and unstructured nature of adipose tissue depots¹⁷, which has proven difficult to molecularly dissect using classical approaches such as fluorescence-activated cell sorting and Cre-lox lines based on candidate marker genes^16,18. Here, using the resolving power of single-cell transcriptomics¹⁹ in a mouse model, we reveal distinct subpopulations of adipose stem and precursor cells in the stromal vascular fraction of subcutaneous adipose tissue. We identify one of these subpopulations as CD142⁺ adipogenesis-regulatory cells, which can suppress adipocyte formation in vivo and in vitro in a paracrine manner. We show that adipogenesis-regulatory cells are refractory to adipogenesis and that they are functionally conserved in humans. Our findings point to a potentially critical role for adipogenesis-regulatory cells in modulating adipose tissue plasticity, which is linked to metabolic control, differential insulin sensitivity and type 2 diabetes.