Characterizing human adipose stem and precursor cells at the single nucleus level in obese and diabetic patients

Swiss partners

• EPFL: Bart Deplancke (main applicant), Carles Canto

Partners in the MENA region

• Sidra Medicine, Qatar: Meritxell Espino-Guarch (main applicant), Nicholas van Panhuys

Presentation of the projet

Obesity is one of the world’s largest health problems, constituting a major risk factor for several of the world’s leading causes of death, including heart disease, stroke, diabetes and cancer. Globally, >39% of adults are overweight, and countries in North-Africa and the Middle East suffer from some of the biggest increases in obesity rates worldwide.

Obesity constitutes an excess accumulation of fat, which, under physiological conditions, is stored in white adipose tissue (WAT) depots in specialized cell types called adipocytes. Adipose depots expand via an increase in adipocyte size (hypertrophy) and/or number (hyperplasia). The expansion capacity of WAT depots is intimately linked to the metabolic health status of an individual. Indeed, obesity is associated with impaired WAT expansion and increased inflammation and AT fibrosis, which results in the deposition of lipids in other organs, leading to metabolic derangements. Adipocyte numbers are controlled by the engagement of adipose stem and progenitor cells (ASPCs) to differentiate into new adipocytes. Our laboratory has pioneered the study of ASPC subpopulations in different fat depots at the single cell transcriptomic level, leading, for example, to the identification of cell types within the ASPC niche that can control adipogenesis in a paracrine manner. However, how ASPC subpopulations are affected at different stages of obesity, most notably between healthy obese patients and those displaying metabolic complications, is still poorly understood.

Through this grant, we aim to collaborate with the Sidra Medicine in Qatar, which has been collecting human fat biopsies from control, healthy obese, prediabetic and type 2 diabetic patients. From these biopsies, a cellular fraction containing ASPCs was isolated and frozen, which we now aim to analyze using single nuclei transcriptomics (snRNA-seq). This will allow us to evaluate how obesity and diabetes functionally influence specific ASPC subpopulations. In addition, we intend to integrate our ASPC snRNA-seq data with other single cell and histological datasets that are being generated in our lab and in Sidra Medicine, allowing to evaluate how compositional and/or molecular changes in APSCs correlate with adipocyte size and number, as well as AT inflammation, in diverse disease stages. Thus, the proposed studies will contribute to an increased understanding of the biology and functional relevance of multiple ASPC subtypes in health and disease.