Molecular mechanisms of T cell senescence through transcriptomics
Background T cell senescence is one of the key components of immunosenescence,closely associated with the occurrence and development of various age-related diseases and tumors.However,there is a lack of research exploring the molecular mechanisms of T cell senescence based on transcriptomics.Objective To establish a T cell senescence model and perform transcriptome sequencing,then use bioinformatics methods to analyze potential molecular mechanisms and identify key genes during T cell senescence.Methods T cells were isolated from human peripheral blood mononuclear cells,after a brief period of in vitro culture for expansion,the cells were randomly divided into senescent T cell group,cultured in a medium containing 20mg/mL D-galactose,and normal control group,cultured in a medium without D-galactose.After 48 hours of culture,changes in telomerase activity,telomere length,senescence-associated secretory phenotype,and β-galactosidase activity were assessed in T cells before and after cell senescence.mRNA transcriptome sequencing of the cell models was performed,and bioinformatics methods were used to analyze significantly differentially expressed genes(DEGs).Enrichment analysis and the construction of protein-protein interaction(PPI)networks were conducted on the DEGs to analyze the functional status of DEGs during T cell senescence and to screen for key genes.Results After 48 hours of D-galactose treatment,T cells showed impaired telomere function,increased expression of p21 gene and protein,increased secretion of cytokines,enhanced β-galactosidase activity,and increased intracellular lipid synthesis.Enrichment analysis revealed that senescent T cells showed enhanced activity in cytokine-cytokine receptor interaction,p53,PI3K/Akt/mTOR,NF-kappaB signaling pathways.PPI network analysis suggested that ISGs and RPs gene families might play a crucial role in T cell senescence.Conclusion Senescent T cells exhibit telomere dysfunction,lipid metabolism disorder,enhanced pro-inflammatory capacity,and increased activity of cell senescence-related signaling pathways.Moreover,the ISGs and RPs gene families may play significant roles in the process of T cell senescence.
T cell senescenceimmunosenescencetelomerelipid metabolismbioinformatics
国家科技期刊平台
NSTL
万方数据
