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.
Highlights
Stem cells can be isolated at all stages of ontogeny, from the early developing embryo to the post-reproductive adult organism
Results of gene set enrichment analysis (GSEA) for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that most upregulated differentially expressed genes (DEGs) in adult bone marrow mesenchymal stem cells (aMSCs) were related to immune-related diseases (Figure 2A), and down-regulated DEGs were abundant in the cell cycle, ribosome pathway, and spliceosome pathway (Figure 2C)
The interferon response and myogenesis were enriched in aMSCs (Figure 2B)
Summary
Stem cells can be isolated at all stages of ontogeny, from the early developing embryo to the post-reproductive adult organism. Adult bone marrow was the first source of mesenchymal stem cells (MSCs) to be identified and is still by far the best characterized (Friedenstein et al, 1987; Kolf et al, 2007; Lv et al, 2014). These cells hold great promise as seed cells in tissue engineering and regenerative medicine, based on their selfrenewal, multi-differentiation, and immunoregulation abilities (Dogan et al, 2014; Wei et al, 2015; Castagnini et al, 2016; Mehrabani et al, 2016). MSCs may undergo senescence, as well as impaired function during ex vivo expansion (Turinetto et al, 2016)
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