JSOG Presenter: Multi-omics Analysis of Stem Cells Established From Aged Individuals to Seek Aging Regulatory Factors [ID 3398]

INTRODUCTION: Assisted reproductive technology (ART) has become increasingly important due to the declining birth rate. However, ART is not immune to the effects of aging, and improving embryo quality in aged donors is a major issue. Therefore, we established embryonic stem cells (ESCs) from blastocysts and induced pluripotent stem cells (iPSCs) from isogenic individuals in order to examine the effects of aging on stem cells in detail. METHODS: Embryonic stem cells and iPSCs from 6-week-old mice up to 24-month-old mice were established, and multi-omics analysis, gene ontology analysis, and radiation-induced genome stability test were performed to identify aging regulatory factors. RESULTS: Transcriptomic analysis followed by gene ontology analysis revealed changes in the expression of genes involved in the cell cycle process; expression of genes involved in genome instability changed, while expression of zygotic gene activation (ZGA) genes increased in aged stem cells. Accordingly, the radiation-induced genome stability test showed that the number of phosphorylation of H2AX (γH2AX, a marker of DNA damage) foci in iPSCs significantly increased with aging, suggesting increased genomic instability. Furthermore, when ZGA genes are knocked down through small hairpin RNA mediation, the number of γH2AX foci in iPSCs slightly decreased in aged iPSCs. CONCLUSIONS/IMPLICATIONS: These results suggest the existence of a compensatory gene cluster in aged stem cells, which might compensate the aging effect in aged stem cells. Restoring the developmental potential of aged embryos might be a breakthrough for better outcomes in ART.