Author Interviews, Brigham & Women's - Harvard, Nature, Weight Research / 05.05.2020 Interview with: Ronald Kahn, MD Chief Academic Officer, Joslin Diabetes Center Mary K. Iacocca Professor of Medicine Harvard Medical School What is the background for this study? What are the main findings? Response: Adipose tissue is a heterogeneous organ and composed of several cell types, including mature adipocytes, preadipocytes, stem cells, endothelial cells, and various blood cells. Different adipose depots have distinct physiological functions associated with their anatomical location and cell composition. For example, accumulation of intra-abdominal (visceral) white adipose tissue is associated with insulin resistance and metabolic syndrome, whereas accumulation of subcutaneous adipose tissue is not metabolically detrimental and may be even associated with increased insulin sensitivity. Determining the mechanisms for these phenotypic differences could lead to development of novel therapies for diabetes, obesity, and their associated morbidities. A central challenging question in research of metabolic disease is whether disease risk for diabetes and metabolic syndrome is driven by a subset of fat cells that may interact with environmental stresses in disease pathogenesis in a way different from other fat cells. Indeed, previous studies from the Kahn lab have shown different fat cells in a single depot from the mouse may exhibit developmental heterogeneity. In this new study, we attempted to address this question for human white fat using a synergistic application of several methodologies: 1) single cell transcriptional profiling of human white fat during differentiation, 2) analysis of individual clones of white fat cells taken from humans at surgery, 3) novel computer based network analysis and 4) integration of the gene signatures across experimental models. Single-cell RNA sequencing is an ideal technique to profile gene expression of heterogeneous cell populations obtained from a single tissue, including fat tissue. (more…)