Whole-transcriptome profiling reveals potential biomarkers for the reversal of thymic epithelial cell senescence by...

Area of Science:

• Immunology
• Stem Cell Biology
• Aging Research

Background:

• Thymic epithelial cell (TEC) dysfunction contributes to thymic degeneration.
• Umbilical cord mesenchymal stem cells (UCMSCs) have shown potential in reversing thymus aging.
• The precise transcriptomic mechanisms underlying UCMSC effects on TECs remain unclear.

Purpose of the Study:

• To investigate the transcriptomic regulation mechanism by which UCMSCs reverse TEC senescence.
• To identify key genes and signaling pathways involved in UCMSC-mediated rejuvenation of aged TECs.

Main Methods:

• Induction of TEC senescence using H2O2, followed by co-culture with UCMSCs.
• Analysis of senescence markers (SA-β-gal, P16, Ki67).
• Transcriptomic sequencing (lncRNA, mRNA, miRNA) and construction of a competitive endogenous regulatory network (ceRNA).
• Validation of key genes using RT-qPCR, immunofluorescence, and western blot.

Main Results:

• UCMSC co-culture reversed H2O2-induced TEC senescence.
• Significant differential expression of mRNAs, lncRNAs, and miRNAs was observed and reversed by UCMSCs.
• The PI3K-AKT signaling pathway was identified as a key pathway regulated by ceRNA.
• UCMSC co-culture upregulated VEGFA, activated PI3K-AKT signaling, downregulated P27, and upregulated CDK2 and CCNE.

Conclusions:

• UCMSC co-culture rejuvenates senescent TECs by activating the PI3K-AKT pathway.
• This activation involves VEGFA upregulation and modulation of cell cycle regulators (P27, CDK2, CCNE).
• UCMSC treatment promotes TEC proliferation and offers a potential therapeutic strategy for thymic aging.