Project description:The cellular complexity of adipose tissue plays a critical role in the pathogenesis of metabolic disease; however, mechanisms underlying adipose dysfunction remain poorly understood. Here, we constructed a single-nucleus and bulk transcriptomic atlas of human visceral adipose tissues from an ethnically homogeneous cohort with defined metabolic states: lean with normal glucose tolerance, obesity, and obesity with type 2 diabetes. Single-nucleus RNA sequencing (snRNA-seq) revealed a fibro-inflammatory subpopulation of adipose stem cells and adipocytes characterized by high THBS1 expression, which were enriched in individuals with obesity and obesity with type 2 diabetes compared to lean controls. Through complementary in vitro, ex vivo, and in vivo experiments, we demonstrated that THBS1 promoted adipose fibrosis and inflammation via macrophage-mediated TGFbeta activation, impairing adipogenesis and adipocyte function. Inhibition of THBS1 attenuated fibro-inflammatory features in metabolically dysfunctional adipose tissues. Collectively, this dataset provides a cellular atlas of human visceral adipose tissue across metabolic disease states and identifies THBS1 as a key pathogenic driver and potential therapeutic target.
Project description:We analyze the contribution of alternative splicing to the transcriptional complexity in adipose tissue and the development of diet-induced obesity. We use Next generation sequencing analysis of mice fed with a control chow diet or a high fat diet.
Project description:We analyze the contribution of alternative splicing to the transcriptional complexity in adipose tissue and the development of diet-induced obesity. We use Next generation sequencing analysis of eWAT from control and Nova1 and Nova2-deficient mice fed with a control diet
Project description:We analyze the contribution of alternative splicing to the transcriptional complexity in adipose tissue and the development of diet-induced obesity. We use Next generation sequencing analysis of eWAT from control and Nova1 and Nova2-deficient mice fed with a high fat diet.