Abstract
BackgroundIncreased 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.MethodsWe 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.ResultsA 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.ConclusionOur 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.
Highlights
Adipocyte hypertrophy and hyperplasia both lead to an increase in adiposity, which in turn gives rise to obesity
32 upstream transcription factors (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
A strong hypothetical functional interaction was observed among these TFs, which supports their common role in the downstream regulation of gene expression during adipogenesis
Summary
Adipocyte hypertrophy (increased adipocyte size) and hyperplasia (increased number of adipocytes) both lead to an increase in adiposity, which in turn gives rise to obesity. Obese individuals are at a greater risk of developing cardiovascular disease, type 2 diabetes, and cancer than their nonobese counterparts (Stephens 2012). Understanding the mechanisms that lead to adipocyte hypertrophy and/or hyperplasia at the transcriptome level a 2017 University of Pretoria. 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). 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
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