Transcriptomic analysis reveals regulation of adipogenesis via long non-coding RNA, alternative splicing, and alternative polyadenylation
Obesity is characterized by dysregulated adipogenesis leading to increased number and/or size of adipocytes. Understanding the molecular mechanisms governing regulation of adipogenesis is therefore key to designing therapeutic interventions against obesity. In our study, we analyzed 3'-end sequencing data generated from sequencing of human preadipocytes and adipocytes, as well as data available in publicly available databases, to propose mechanisms of molecular regulation of adipogenesis. We discovered lncRNAs that have not been previously characterized but may be key regulators of both brown and white adipogenesis. We also demonstrated possible mechanisms of direct or indirect regulation of adipogenesis through alternative splicing. Finally, we show that usage of alternative polyadenylation sites of key adipogenesis genes leads to isoform diversity, which can have significant biological consequences on differentiation efficiency. Therefore, our research reveals potential therapeutic avenues for obesity through manipulation of long non-coding RNA levels, alternative splicing as well as the usage of alternative polyadenylation sites. Overall design: To investigate changes in gene expression and alternative polyadenylation during white adipogenesis of primary human preadipocytes (Day 0) to mature adipocytes (Day 14).