Identification of transcription factors potentially involved in human adipogenesis in vitro

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.

Characterising open chromatin in chick embryos identifies cis-regulatory elements important for paraxial mesoderm formation and axis extension

“…2j ). ZNF263 is involved in adipogenesis 39 . The Ewing sarcoma RNA binding protein 1 (EWSR1) regulates gene expression, cell signalling, RNA processing and transport.…”

Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways

“…The process of adipogenesis has been extensively studied and decades of research have reported over a dozen transcription factors to be involved in regulating this process, both in vitro and in vivo [146,147] (Figure 2). The transcription factor Zfp423 plays an essential role in regulating MSC commitment to preadipocytes and its expression remains unchanged during adipogenesis [148,149].…”

“…Other transcription factors such as LIM only domain protein 3 (LMO3), FOXO1 and zinc finger and BTB domain containing 16 (ZBTB16), have been shown to be highly expressed during human adipogenesis in vitro, suggesting a possible role in promoting this process [174]. In silico analysis of genes that were differentially expressed during human adipogenesis in vitro [174] has identified several other transcription factors with possible roles in adipocyte differentiation [146].…”

Characterising open chromatin identifies novel cis-regulatory elements important for paraxial mesoderm formation and axis extension

“…Other TFs enriched identified include TCF12, which is part of the canonical Wnt pathway and implicated as a transcriptional repressor in colorectal cancer (Lee et al, 2012). Specificity proteins (Sp1, Sp2, Sp3 and Sp8) which are known to interact with bHLH proteins such as MyoD (Biesiada et al, 1999); and znf263 a zinc-finger TF involved in adipogenesis (Ambele and Pepper, 2017).…”