EPAS1 prevents telomeric damage induced senescence through enhancing transcription of TRF1, TRF2 and RAD50

In this study, we performed cross-species comparison and identified EPAS1, a well-defined oxygen response gene, to be a key telomeric protector in bat fibroblasts. Bat fibroblasts highly express EPAS1. EPAS1 enhances the transcription of shelterin components TRF1 and TRF2, as well as DNA repairing factor RAD50, conferring bat fibroblasts resistance to senescence in the process of long-term consecutive expansion. Through investigating human single cell transcriptome atlas, we identified that EPAS1 is predominantly expressed in human pulmonary endothelial cell subpopulation. Using in vitro cultured human pulmonary endothelial cells, we confirmed the functional and mechanism conservativeness of EPAS1 in telomeric protection between bat and human. In addition, we explored EPAS1 agonist M1001 to be a protective chemical in coping with bleomycin induced pulmonary telomeric damage and senescence. In summary, we provided a mechanism that could be used to modulate telomeric stability in aging related human pulmonary diseases through learning from long-lived animal bat.