Identification of transcription factors potentially involved in human adipogenesis in vitro

Increased adiposity in humans leads to obesity, which is a major risk factor for cardiovascular disease, type 2 diabetes, and cancer. We previously conducted an extensive unbiased in vitro transcriptomic analysis of adipogenesis, using human adipose-derived stromal cells (ASCs). Here, we have applied computational methods to these data to identify transcription factors (TFs) that constitute the upstream gene regulatory networks potentially, driving adipocyte formation in human ASCs.

We used Affymetrix Transcription Analysis Console™ v3.0 for calculating differentially expressed genes. MATCH™ and F-MATCH™ algorithms for TF identification. STRING v10 to predict protein-protein interactions between TFs.

A number of TFs that were reported to have a significant role in adipogenesis, as well as novel TFs that have not previously been described in this context, were identified. Thus, 32 upstream TFs were identified, with most belonging to the C2H2-type zinc finger and HOX families, which are potentially involved in regulating most of the differentially expressed genes observed during adipocyte differentiation. Furthermore, 17 important upstream TFs were found to have increased regulatory effects on their downstream target genes and were consistently up-regulated during the differentiation process. A strong hypothetical functional interaction was observed among these TFs, which supports their common role in the downstream regulation of gene expression during adipogenesis.

Our results support several previous findings on TFs involved in adipogenesis and thereby validate the comprehensive and systematic in silico approach described in this study. In silico analysis also allowed for the identification of novel regulators of adipocyte differentiation.