| 项目编号 | PRJCA015594 | ||||||||
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| 项目标题 | EPAS1 prevents telomeric damage induced senescence through enhancing transcription of TRF1, TRF2 and RAD50 | ||||||||
| 涉及领域 | senescence | ||||||||
| 数据类型 |
Transcriptome or Gene expression
Raw sequence reads |
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| 物种名称 |
Mus musculus
Rhinolophus sinicus |
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| 描述信息 | Telomeres are nucleoprotein structures at the end of each chromosome functioning to terminal protection and genomic stability. Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo. As long-lived mammals based on body size, bats displays unique telomeric patterns with unknown molecular mechanisms. 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 fibroblast. 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 process of long-term consecutive expansion. Through investigating human single cell transcriptome atlas, we identified that EPAS1 is predominantly expressed in pulmonary endothelial cell subpopulation of human lung. Using in vitro cultured human pulmonary endothelial cells, we confirmed the functional and mechanistic 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 ageing related human pulmonary diseases through learning from long-lived animal bat. | ||||||||
| 样品范围 | Multispecies | ||||||||
| 发布日期 | 2023-03-27 | ||||||||
| 项目资金来源 |
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| 提交者 | Bo Zhao (kiz_zhaolab@163.com) | ||||||||
| 提交单位 | Kunming Institute of Zoology, Chinese Academy of Sciences | ||||||||
| 提交日期 | 2023-03-16 |