Analysis of Hub Genes Involved in Distinction Between Aged and Fetal Bone Marrow Mesenchymal Stem Cells by Robust Rank Aggregation and Multiple Functional Annotation Methods

Xiaoyao Liu; Mingjing Yin; Xinpeng Liu; Junlong Da; Kai Zhang; Xinjian Zhang; Lixue Liu; Jianqun Wang; Han Jin; Zhongshuang Liu; Bin Zhang; Ying Li

doi:10.3389/fgene.2020.573877

Analysis of Hub Genes Involved in Distinction Between Aged and Fetal Bone Marrow Mesenchymal Stem Cells by Robust Rank Aggregation and Multiple Functional Annotation Methods

Front Genet. 2020 Dec 14:11:573877. doi: 10.3389/fgene.2020.573877. eCollection 2020.

Authors

Xiaoyao Liu¹, Mingjing Yin¹, Xinpeng Liu¹, Junlong Da¹, Kai Zhang¹, Xinjian Zhang¹, Lixue Liu¹, Jianqun Wang¹, Han Jin¹, Zhongshuang Liu¹, Bin Zhang^{1

2}, Ying Li¹

Affiliations

¹ Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
² Heilongjiang Academy of Medical Sciences, Harbin, China.

Abstract

Stem cells from fetal tissue protect against aging and possess greater proliferative capacity than their adult counterparts. These cells can more readily expand in vitro and senesce later in culture. However, the underlying molecular mechanisms for these differences are still not fully understood. In this study, we used a robust rank aggregation (RRA) method to discover robust differentially expressed genes (DEGs) between fetal bone marrow mesenchymal stem cells (fMSCs) and aged adult bone marrow mesenchymal stem cells (aMSCs). Multiple methods, including gene set enrichment analysis (GSEA), Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation of the robust DEGs, and the results were visualized using the R software. The hub genes and other genes with which they interacted directly were detected by protein-protein interaction (PPI) network analysis. Correlation of gene expression was measured by Pearson correlation coefficient. A total of 388 up-regulated and 289 down-regulated DEGs were identified between aMSCs and fMSCs. We found that the down-regulated genes were mainly involved in the cell cycle, telomerase activity, and stem cell proliferation. The up-regulated DEGs were associated with cell adhesion molecules, extracellular matrix (ECM)-receptor interactions, and the immune response. We screened out four hub genes, MYC, KIF20A, HLA-DRA, and HLA-DPA1, through PPI-network analysis. The MYC gene was negatively correlated with TXNIP, an age-related gene, and KIF20A was extensively involved in the cell cycle. The results suggested that MSCs derived from the bone marrow of an elderly donor present a pro-inflammatory phenotype compared with that of fMSCs, and the HLA-DRA and HLA-DPA1 genes are related to the immune response. These findings provide new insights into the differences between aMSCs and fMSCs and may suggest novel strategies for ex vivo expansion and application of adult MSCs.

Keywords: adult setm cell; bone marrow mesenchymal stem cell; fetal stem cell; hub genes; robust rank aggregation.