Volume 44 Issue 3
May  2023
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Kai-Qin Li, Gao-Jing Liu, Xiu-Yun Liu, Qiong-Fang Chen, Xiao-Yan Huang, Qiu Tu, Jiao Zhang, Qing Chang, Yun-Hua Xie, Rong Hua, Dong-Ming Xu, Zhen Liu, Bo Zhao. EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50. Zoological Research, 2023, 44(3): 636-649. doi: 10.24272/j.issn.2095-8137.2022.531
Citation: Kai-Qin Li, Gao-Jing Liu, Xiu-Yun Liu, Qiong-Fang Chen, Xiao-Yan Huang, Qiu Tu, Jiao Zhang, Qing Chang, Yun-Hua Xie, Rong Hua, Dong-Ming Xu, Zhen Liu, Bo Zhao. EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50. Zoological Research, 2023, 44(3): 636-649. doi: 10.24272/j.issn.2095-8137.2022.531

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

doi: 10.24272/j.issn.2095-8137.2022.531
The RNA-seq data are available at the NCBI Gene Expression Omnibus (GEO) under accession No. SRR18461285–90, GSA at the National Genomics Data Center under accession No. PRJCA015594, and Science Data Bank under DOI: 10.57760/sciencedb.07762. All other data supporting the findings of this study are available from the corresponding author upon reasonable request.
Supplementary data to this article can be found online.
B.Z. and K.Q.L. are co-inventors of a patent application covering the use of EPAS1 agonists to stabilize telomeres in vivo and benefit health span. All other authors declare no competing interests.
K.Q.L., X.Y.L., Q.F.C., X.Y.H., Q.T., J.Z., Q.C., Y.H.X., and R.H. performed the experiments and analyzed the data. G.J.L., D.M.X., and Z.L. performed the bioinformatics and statistical analyses. B.Z. and K.Q.L. designed the experiments. B.Z. supervised the studies. B.Z. and K.Q.L. wrote the paper. B.Z. conceived the study. All authors read and approved the final version of the manuscript.
#Authors contributed equally to this work
Funds:  This work was supported by the Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province (202201AS070044), National Key Research & Developmental Program of China (2021YFA0805701), Chinese Academy of Sciences (CAS) “Light of West China” Program (xbzg-zdsys-202113), and Kunming Science and Technology Bureau (2022SCP007)
More Information
  • Corresponding author: E-mail: zhaobo@mail.kiz.ac.cn
  • Received Date: 2023-02-23
  • Accepted Date: 2023-04-11
  • Published Online: 2023-04-17
  • Publish Date: 2023-05-18
  • Telomeres are nucleoprotein structures located at the end of each chromosome, which function in terminal protection and genomic stability. Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo. As relatively long-lived mammals based on body size, bats display unique telomeric patterns, including the up-regulation of genes involved in alternative lengthening of telomeres (ALT), DNA repair, and DNA replication. At present, however, the relevant molecular mechanisms remain unclear. In this study, we performed cross-species comparison and identified EPAS1, a well-defined oxygen response gene, as a key telomeric protector in bat fibroblasts. Bat fibroblasts showed high expression of EPAS1, which enhanced the transcription of shelterin components TRF1 and TRF2, as well as DNA repair factor RAD50, conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion. Based on a human single-cell transcriptome atlas, we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation. Using in vitro-cultured human pulmonary endothelial cells, we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans. In addition, the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence. In conclusion, we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging, drawing insights from the longevity of bats.
  • The RNA-seq data are available at the NCBI Gene Expression Omnibus (GEO) under accession No. SRR18461285–90, GSA at the National Genomics Data Center under accession No. PRJCA015594, and Science Data Bank under DOI: 10.57760/sciencedb.07762. All other data supporting the findings of this study are available from the corresponding author upon reasonable request.
    Supplementary data to this article can be found online.
    B.Z. and K.Q.L. are co-inventors of a patent application covering the use of EPAS1 agonists to stabilize telomeres in vivo and benefit health span. All other authors declare no competing interests.
    K.Q.L., X.Y.L., Q.F.C., X.Y.H., Q.T., J.Z., Q.C., Y.H.X., and R.H. performed the experiments and analyzed the data. G.J.L., D.M.X., and Z.L. performed the bioinformatics and statistical analyses. B.Z. and K.Q.L. designed the experiments. B.Z. supervised the studies. B.Z. and K.Q.L. wrote the paper. B.Z. conceived the study. All authors read and approved the final version of the manuscript.
    #Authors contributed equally to this work
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