BACKGROUND : 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. METHODS : We used Affymetrix Transcription Analysis ConsoleTM v3.0 for calculating differentially
expressed genes. MATCHTM and F-MATCHTM algorithms for TF
identification. STRING v10 to predict protein–protein interactions between
TFs. RESULTS : 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. CONCLUSION : Our results support several previous findings on TFs involved in adipogenesi 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.
Table S1. A complete list of differentially expressed genes
on day 1.
Table S2. A complete list of differentially expressed genes
on day 7.
Table S3. A complete list of differentially expressed genes
on day 14.
Table S4. A complete list of differentially expressed genes
on day 21.