Features and mechanisms of long-lived Myotis somatic fibroblasts in response to DNA replication stressOACSCDCSTPCD
The DNA replication stress(RS)response is crucial for maintaining cellular homeostasis and promoting physiological longevity.However,the mechanisms by which long-lived species,such as bats,regulate RS to maintain genomic stability remain unclear.Also,recent studies have uncovered noncanonical roles of ribosome-associated factors in maintaining genomic stability.In this study,somatic skin fibroblasts from the long-lived big-footed bat(Myotis pilosus)were examined,with results showing that bat cells exhibited enhanced RS tolerance compared to mouse cells.Comparative transcriptome analysis under RS conditions revealed pronounced species-specific transcriptional differences,including robust up-regulation of ribosome biogenesis genes in bat cells and a markedly reduced activation of the P53 signaling pathway.These features emphasize a distinct homeostatic strategy in bat cells.Nuclear fragile X mental retardation-interacting protein 1(Nufip1),a ribosome-associated factor highly expressed in bat fibroblasts,was identified as a potential integrator of ribosomal and P53 signaling via its association with ribosomal protein S27-like(Rps27l).These findings provide direct cellular and molecular evidence for a noncanonical RS response in bats,highlighting a deeper understanding of the biological characteristics and genomic maintenance mechanisms of long-lived species.
Xiao-Yan Huang;Xiu-Yun Liu;Wei Wang;Gao-Jing Liu;You-Long Zhu;Xiao Wen;Kai-Qin Li;Bo Zhao
Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key Laboratory of Genetic Evolution&Animal Models,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key laboratory of Animal Models and Human Disease Mechanisms,Chinese Academy of Sciences,Kunming,Yunnan 650201,China University of Chinese Academy of Sciences,Beijing 100049,ChinaKunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key Laboratory of Genetic Evolution&Animal Models,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key laboratory of Animal Models and Human Disease Mechanisms,Chinese Academy of Sciences,Kunming,Yunnan 650201,China University of Chinese Academy of Sciences,Beijing 100049,ChinaKunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key Laboratory of Genetic Evolution&Animal Models,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key laboratory of Animal Models and Human Disease Mechanisms,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province,and KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases,Kunming,Yunnan 650201,ChinaKunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key Laboratory of Genetic Evolution&Animal Models,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key laboratory of Animal Models and Human Disease Mechanisms,Chinese Academy of Sciences,Kunming,Yunnan 650201,China University of Chinese Academy of Sciences,Beijing 100049,ChinaDepartment of Hepatobiliary and Pancreatic Surgery,Second Affiliated Hospital of Kunming Medical University,Kunming,Yunnan 650033,ChinaKunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key Laboratory of Genetic Evolution&Animal Models,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key laboratory of Animal Models and Human Disease Mechanisms,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province,and KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases,Kunming,Yunnan 650201,ChinaKunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key Laboratory of Genetic Evolution&Animal Models,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key laboratory of Animal Models and Human Disease Mechanisms,Chinese Academy of Sciences,Kunming,Yunnan 650201,ChinaKunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key Laboratory of Genetic Evolution&Animal Models,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key laboratory of Animal Models and Human Disease Mechanisms,Chinese Academy of Sciences,Kunming,Yunnan 650201,China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province,and KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases,Kunming,Yunnan 650201,China University of Chinese Academy of Sciences,Beijing 100049,China Primate Facility,National Research Facility for Phenotypic&Genetic Analysis of Model Animals,and National Resource Center for Non-Human Primates,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China
生物科学
Long-lived speciesMyotis pilosusDNA replication stressRibosome biogenesisP53 signalingNufip1Rps27l
《Zoological Research》 2025 (3)
P.709-721,13
supported by the Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province(202401AT070186 to K.Q.L.,202201AS070044 to B.Z.)Yunnan Province(202305AH340006 to B.Z.)Kunming Science and Technology Bureau(2022SCP007 to B.Z.)。
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