Co-expression network analysis identified key genes in association with mesenchymal stem cell osteogenic differentiation

Cell Tissue Res. 2019 Dec;378(3):513-529. doi: 10.1007/s00441-019-03071-1. Epub 2019 Aug 15.

Abstract

Although several studies have shown that osteogenic differentiation of different mesenchymal stem cell (MSC) lines can be guided by the 3D scaffold with growth factors or biochemical agent, the key mechanism regulating osteogenic differentiation is not known yet. Here, this study was designed to investigate key genes that regulate the induction of osteogenesis by different MSC lines in different ways. Expression profiling by array (GSE58919 and GSE18043) was downloaded and analyzed using weighted gene co-expression network analysis (WGCNA) to narrow genes associated with osteogenic differentiation. A protein-protein interactive (PPI) network was built to find the key genes and the role of these key genes was confirmed by statistical analysis. To understand the function of genes associated with osteogenesis, gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) were analyzed, which showed that key genes in MSC osteogenic differentiation induced by a biochemical agent involve regulation of cell apoptosis and proliferation while key genes in MSC osteogenic differentiation induced by the 3D scaffold with growth factors involve regulation of cajal body and centromeres. Furthermore, 58 key genes are involved in Wnt signaling pathway, ion response and focal adhesion. Proteasome also played a key role in osteogenic differentiation. Seven potential key genes were found essential in the osteogenic differentiation of MSCs in the PPI network, especially the five key genes, CCT2, NOP58, FBL, EXOSC8 and SNRPD1. This study will provide important targets of MSC osteogenic differentiation that will help us understand the mechanism of osteogenic differentiation in MSCs.

Keywords: Different cultural method; GEO; Mesenchymal stem cells; Osteogenic differentiation; WGCNA.

MeSH terms

  • Biological Transport, Active
  • Cell Adhesion
  • Cell Differentiation
  • Cell Line
  • Databases, Genetic
  • Gene Regulatory Networks
  • Humans
  • Ion Transport
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Osteogenesis / genetics*
  • Wnt Signaling Pathway