RNA sequencing profiles reveal dynamic signaling and glucose metabolic features during bone marrow mesenchymal stem cell senescence

Abstract

Background Stem cell senescence is considered as a significant driver of organismal aging. As individuals age, the number of stem cells is declined, and the ability to proliferate and survive is also weakened. It has been reported that metabolism plays an important role in stem cell self-renewal, multilineage differentiation, senescence and fate determination, which has aroused widespread concerns. However, whether metabolism-related genes or signalling pathways are involved in physiological aging remain largely undetermined. Results In the current study, we showed 868 up-regulated and 2006 down-regulated differentially expressed genes (DEGs) in bone marrow mesenchymal stem cells (MSCs) from old rats in comparison with that from young rats by performing RNA sequence. And DEGs functions and pathways were further selected by function enrichment analysis. The results indicated that the high expression of DEGs might participate in cell differentiation, growth factor binding and etc., while the down-regulated DEGs were majorly enriched in metabolism process, such as the cellular metabolic process and mitochondria. Then, we screened and verified DEGs related to glucose metabolism and investigated the glycolysis levels. We identified that glucose uptake, lactate secretion, ATP production and relative extracellular acidification rates (ECAR) were all diminished in MSCs from old rats. More importantly, we conducted microRNA prediction on the key DEGs of glycolysis to elucidate the potential molecular mechanisms of glucose metabolism affecting MSC senescence. Conclusions Our study unravelled the profiles of DEGs in age-associated MSC senescence and their functions and pathways. We also clarified DEGs related to glucose metabolism and down-regulated glycolysis level in age-associated MSC senescence. This study will uncover the metabolic effects on regulating stem cell senescence, and provide novel therapeutic targets for ameliorating age-associated phenotypes.

Mechanical Rejuvenation of Mesenchymal Stem Cells from Aged Patients

“…Previous studies have demonstrated that gene expression related to metabolic processes and protein/nucleotide biosynthetic processes are markedly downregulated in BM-MSCs from aged donors, supporting the critical role of metabolism in regulating stem cell senescence. 63 KEGG pathway analysis further revealed a significant upregulation of biosynthesis of unsaturated fatty acids pathways in the brachial-treated group, which has been previously reported to be enriched in young, healthy MSCs (SI Fig. 6) .…”

Nicotinamide Mononucleotide Supplementation Improves Mitochondrial Dysfunction and Rescues Cellular Senescence by NAD+/Sirt3 Pathway in Mesenchymal Stem Cells

“…In our previous study, cell surface antigens were used to identify obtained MSCs by flow cytometry. We found that serial expanded MSCs are positive for mesenchymal progenitor markers including CD44, CD90, and CD105, and negative for CD31 and CD45 [ 32 ]. Nevertheless, MSCs at LP presented attenuated osteogenesis compared with EP MSCs [ 17 ].…”

“…MSCs were obtained according to a previously described method [ 16 , 17 , 32 ]. Primary MSCs derived from healthy, 1–2-month-old male Wistar rats were isolated by the whole bone marrow adherent method.…”

Mesenchymal Stem Cell Senescence during Aging:From Mechanisms to Rejuvenation Strategies

“…What’s more, an examination of BM-MSCs from old and young rats revealed 868 differentially expressed genes (DEGs) that were up-regulated and 2006 that were down-regulated. A high expression of DEGs might be involved in cell differentiation and growth factor binding, whereas down-regulated DEGs appear to be involved in metabolism [ 55 ]. Circular RNAs(circRNAs) may compete with microRNAs (miRNAs) for the ability to stabilize or translate target RNAs, and thereby affect gene expression.…”