AUTHOR=Mathur Neha , Severinsen Mai C. K. , Jensen Mette E. , Naver Lars , Schrölkamp Maren , Laye Matthew J. , Watt Matthew J. , Nielsen Søren , Krogh-Madsen Rikke , Pedersen Bente Klarlund , Scheele Camilla TITLE=Human visceral and subcutaneous adipose stem and progenitor cells retain depot-specific adipogenic properties during obesity JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=Volume 10 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.983899 DOI=10.3389/fcell.2022.983899 ISSN=2296-634X ABSTRACT=Abdominal obesity associates with cardiometabolic disease and an accumulation of lipids in the visceral adipose depot, whereas lipid accumulation in the subcutaneous depot is more benign. We aimed to further investigate whether the adipogenic properties where cell-intrinsic, or dependent on a depot-specific or obesity-produced microenvironment. We obtained visceral and subcutaneous biopsies from non-obese women (n=13) or women living with morbid obesity (n=13) and derived adipose stem and progenitor cell cultures from the stromal vascular fraction. Following in vitro differentiation, we observed a contrasting pattern with a lower gene expression of adipogenic markers and a higher gene expression of immunogenic markers in the visceral compared to the subcutaneous adipocytes. We identified the immunogenic factor BST2 as a marker for visceral adipose stem and progenitor cells. Differentiation with exogenous Tumor necrosis factor resulted in increased immunogenic signatures and decreased adipogenic signatures in cells from both depots. The effect of obesity in was minor. Our data, from 26 women, underscore the intrinsic differences between human visceral and subcutaneous adipose stem and progenitor cells, suggest that dysregulation of adipocytes in obesity mainly occurs at a post-progenitor stage, and highlight an inflammatory microenvironment as a major constraint of human adipogenesis.