Dynamic changes in the gene expression during adipogenesis in hMSCs

Abstract

Obesity results due to accumulation of adipose tissue mass, arising either from an increase in the size (hypertrophy) and/or number (hyperplasia) of adipocytes. The knowledge of detailed molecular mechanisms that govern the adipogenesis is necessary to understand the development of obesity. In this study we have generated RNA seq data from differentiating hMSCs on day 0, 4, 8 and 16 and analysed it to understand differential gene expression during adipogenesis. Gene ontology (GO) analysis showed that lipid metabolism and ‘oxidation–reduction’ reactions were important to the entire process of adipogenesis. Gene set enrichment analysis revealed that the upregulated differentially expressed genes (DEGs) were related to PPAR (peroxisome proliferator-activated receptor) signalling, adipogenesis, adipocytokine signalling, fatty acid metabolism pathways and downregulated DEGs were from myogenesis, calcium signalling, ERBB signalling, TGFβ signalling pathways considered as antiadipogenic. Further, our analysis of molecular network of two important transcription factors of adipogenesis, namely, PPARγ and CEBPα revealed that total number of interactions with their activators increased while that with inhibitors decreased throughout adipogenesis. These data clearly demonstrate changes in gene expression driving adipogenesis and could be used in the development of therapeutics to control obesity.