Wnt signaling preserves progenitor cell multipotency during adipose tissue development

Zinger Yang Loureiro, Shannon Joyce, Tiffany DeSouza, Javier Solivan-Rivera, Anand Desai, Pantos Skritakis, Qin Yang, Rachel Ziegler, Denise Zhong, Tammy T. Nguyen, Ormond A. MacDougald & Silvia Corvera 

Nat Metab 5, 1014–1028 (2023). https://doi.org/10.1038/s42255-023-00813-y

Mesenchymal stem/progenitor cells are essential for tissue development and repair throughout life, but how they are maintained under chronic differentiation pressure is not known. Using single-cell transcriptomics of human progenitor cells we find that adipose differentiation stimuli elicit two cellular trajectories: one toward mature adipocytes and another toward a pool of non-differentiated cells that maintain progenitor characteristics. These cells are induced by transient Wnt pathway activation and express numerous extracellular matrix genes and are therefore named structural Wnt-regulated adipose tissue cells. We find that the genetic signature of structural Wnt-regulated adipose tissue cells is present in adult human adipose tissue and adipose tissue developed from human progenitor cells in mice. Our results suggest a mechanism whereby adipose differentiation occurs concurrently with the maintenance of a mesenchymal progenitor cell pool, ensuring tissue development, repair and appropriate metabolic control over the lifetime.