Researchers working in mice and human tissue have identified several classes of adipocyte progenitor cells, which give rise to fat tissue, some of which reside in a recently discovered anatomical niche. The results may help inform the development of targeted approaches to prevent metabolic diseases. White adipose (fat) tissue plays a key role in metabolic health by storing excess calories while preventing the damaging accumulation of lipids in other tissues and organs. Previous research has shown that white adipose tissue can expand in two ways: adipocytes, or fat cells, can either increase in number or individual cells can increase in size. The latter, called adipocyte hypertrophy, causes fibrosis and inflammation and can promote metabolic diseases like type 2 diabetes. Therefore, metabolic health relies on the ability of adipose tissue progenitor cells (APCs) to become fully fledged fat cells. However, the cellular mechanisms underlying the formation of adipocytes, and the APCs from which they are derived, are incompletely understood. David Merrick and colleagues used single-cell RNA sequencing to identify and profile progenitor cells from the rapidly developing white adipose tissue of 12-day old mice. Merrick et al. identified three classes of APCs. Additional experiments revealed that two general classes of APCs analogous to those found in mice are present in subcutaneous fat tissue in humans. The results suggest a general paradigm for adipogenesis in both mice and humans, the authors say. Intriguingly, in mice, one of the identified progenitor cells - marked by a protein called DPP4 - was found in the reticulum interstitium (RI). This recently recognized anatomical niche is a fluid-filled network of collagen and elastin fibers that surrounds many organs. "Given that the RI exists in multiple human tissues, an intriguing possibility is that the RI represents a new stem cell niche for fat tissue and beyond," write You-Ying Chau and William Cawthron in a related Perspective. They also discuss how the work compares to recent efforts to understand adipose tissue progenitor cells.