Transcriptomic changes in the hypothalamus of rhesus monkeys with bone marrow mesenchymal stem cells treatment

Abstract

Background: It is acknowledged that the hypothalamus plays an important role in the regulation of aging, and bone marrow mesenchymal stem cells (BMSCs) possess an anti-aging effect, this study was therefore designed to investigate transcriptomic changes in the hypothalamus of aged rhesus monkeys with BMSCs-treatment to explore the underlying molecular mechanism for the anti-aging effect of BMSCs. Methods: Transcriptome profiling sequencing was conducted on the juvenile rhesus macaques (YN), adult rhesus macaques (QN), aged rhesus macaques (LN) and BMSCs-treated aged rhesus macaques (ZL). Then, differentially expressed genes (DEG) analysis was performed between YN and QN, QN and LN, LN and ZL, respectively. After the intersection of DEGs from these three pairs of comparisons, screened intersecting genes were subject to GO (Gene Ontology) enrichment analysis, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and PPI (protein-protein interaction) analysis to explore their interactions and underlying mechanism of BMSCs for retarding aging. Lastly, according to the results of PPI and the most enriched GO term, we further integrated and screened genes, which were regarded as aging-related genes in the hypothalamus. Results: According to obtained transcriptome profiling data, 671 differentially expressed genes were screened between QN and YN, 1315 genes between LN and QN, and 1345 genes between ZL and LN. After intersecting, 53 genes were screened out. GO analysis showed that most genes were mainly enriched in intercellular adhesion, sphingosinol biosynthesis, ceramide biosynthesis in BP, while in the cell membrane group and Golgi membrane in CC. PPI suggested that SPTLC2, ASAH2, FA2H and other genes had higher core degrees, indicating these hub genes may be involved in the process of aging by lipid metabolism. After the final screening, a total of 28 genes with significant differences were screened out, among which GPR68, LOC706331, STRA6 and PDE7B were up-regulated in QN and ZL compared with YN and LN respectively, while down-regulated in LN compared with QN. The other 24 genes were down-regulated in QN and ZL compared with YN and LN respectively, while up-regulated in LN compared with QN. Conclusion: A total of 28 genes were recognized as aging-related genes in the hypothalamus, and BMSCs treatment for retarding aging may be involved in these gene targets.