Uncovering the role of adipose tissue fibroblast heterogeneity in health and metabolic disease progression

White adipose tissue (WAT) contains a large and heterogenous population of fibroblasts.

While recent data highlight that these cells are important for organ function by influencing inflammatory processes, adipocyte formation, and extracellular matrix composition, it is not clear how they are perturbed by, and contribute to the development of, different disease states.

In this project, I will capitalize on recently developed assays, including spatial transcriptomics, 3D cell models and mouse-based transplantation experiments, to determine how different fibroblast subpopulations contribute to tissue function and are linked to metabolic diseases. I will achieve this ambitious goal by defining and isolating specific fibroblast subpopulations from clinical cohorts.

These cells will subsequently be studied ex vivo in 3D spheroid models and in vivo by transplanting them into immunodeficient NSG mice.

By editing the cells using CRISPR/Cas9-mediated engineering prior to culture/transplantation, I will identify and study key regulators of cell function.

Together, these results will provide hitherto unprecedented insights into how specific fibroblast subtypes contribute to WAT function in health and metabolic disease.