Screening for genes, transcription factors and miRNAs associated with the myogenic and osteogenic differentiation of human adipose tissue-derived stem cells.

Abstract

In the present study, we aimed to reveal the molecular mechanisms responsible for the differentiation of human adipose tissue-derived stem cells(hASCs) into myocytes and osteoblasts. Microarray data GSE37329 were obtained from the Gene Expression Omnibus database, including three hASC cell lines from healthy donors, two osteogenic lineages and two myogenic lineages from the invitro‑induction of hASCs. Differentially expressed genes(DEGs) in the two lineages were firstly screened. Subsequently, the underlying functions of the two sets of DEGs were investigated by Gene Ontology function and Kyoto Encyclopedia of Genes and Genomespathway enrichment analysis, followed by protein-protein interaction(PPI) network construction. Regulatory relationships between transcription factors(TFs) and microRNAs (miRNAs or miRs) with target genes were finally explored using different algorithms. A total of 665 and 485DEGs were identified from the hASC‑derived myogenic and osteogenic lineages, respectively. The shared upregulated genes (n=205) in the two sets of DEGs were mainly involved in metabolism-related pathways, whereas the shared downregulated genes (n=128) were significantly enriched in the transforming growth factor-β(TGF-β) signaling pathway. Four genes, vascular endothelial growth factorA(VEGFA), fibroblast growth factor2(FGF2), nerve growth factor(NGF) and interleukin1B(IL1B), presented with relatively higher degrees in both PPI networks. The transcription factor RAD21 was predicted to target shared upregulated and downregulated genes as well as specific downregulated genes in the myogenic and the osteogenic lineages. In addition, miRNA-DEG interaction analysis revealed that hsa-miR-1 regulated the most shared DEGs in the two lineages. There may be a correlation between the four genes, VEGFA, FGF2, IL1B and NGF, and the differentiation of hASCs into myocytes and osteoblasts. The TF RAD21 and hsa-miR-1 may play important roles in regulating the expression of differentiation-associated genes.