High altitude is an extreme environment that imposes hypoxic pressure on physiological processes,and natives living at high altitudes are more adaptive in certain physiological processes.So far,epigenetic modification...High altitude is an extreme environment that imposes hypoxic pressure on physiological processes,and natives living at high altitudes are more adaptive in certain physiological processes.So far,epigenetic modifications under extreme changes in hypoxic pressures are relatively less understood.Here,we recruit 32 Tibetan elite alpinists(TEAs),who have successfully mounted Everest(8848 m)at least five times.Blood samples and physiological phenotypes of TEAs and 32 matched non-alpinist Tibetan volunteers(non-TEAs)are collected for analysis.Genome-wide DNA methylation analysis identifies 23,202 differentially methylated CpGs(P_(adj)<0.05,|β|>0.1)between the two groups.Some differentially methylated CpGs are in hypoxia-related genes such as PPP1R13L,MAP3K7CL,SEPTI-9,and CUL2.In addition,Gene ontology enrichment analysis reveals several inflammation-related pathways.Phenotypic analysis indicates that 12 phenotypes are significantly different between the two groups.In particular,TEAs exhibit higher blood oxygen saturation levels and lower neutrophil count,platelet count,and heart rate.For DNA methylation association analysis,we find that two CpGs(cg16687447,cg06947206)upstream of PTEN were associated with platelet count.In conclusion,extreme hypoxia exposure leads to epigenetic modifications and phenotypic alterations of TEA,providing us clues for exploring the molecular mechanism underlying changes under extreme hypoxia conditions.展开更多
基金The Science and Technology Department of Tibet(08080002)2019 School-level Cultivation Project of Tibet University(ZDTSJH19-08)+4 种基金the Special Funds from the Central Finance to Support the Development of Local Universities(ZFYJY201902011.Index of Tibetan Finance and Education[2018]No.54,[2019]No.1-19,[2020]No.79)This work was also supported by the Postdoctoral Science Foundation of China(2018M640333)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)Science and Technology Committee of Shanghai Municipality(18490750300)Major Project of Special Development Funds of Zhangjiang National Independent Innovation Demonstration Zone(ZJ2019-ZD-004).
文摘High altitude is an extreme environment that imposes hypoxic pressure on physiological processes,and natives living at high altitudes are more adaptive in certain physiological processes.So far,epigenetic modifications under extreme changes in hypoxic pressures are relatively less understood.Here,we recruit 32 Tibetan elite alpinists(TEAs),who have successfully mounted Everest(8848 m)at least five times.Blood samples and physiological phenotypes of TEAs and 32 matched non-alpinist Tibetan volunteers(non-TEAs)are collected for analysis.Genome-wide DNA methylation analysis identifies 23,202 differentially methylated CpGs(P_(adj)<0.05,|β|>0.1)between the two groups.Some differentially methylated CpGs are in hypoxia-related genes such as PPP1R13L,MAP3K7CL,SEPTI-9,and CUL2.In addition,Gene ontology enrichment analysis reveals several inflammation-related pathways.Phenotypic analysis indicates that 12 phenotypes are significantly different between the two groups.In particular,TEAs exhibit higher blood oxygen saturation levels and lower neutrophil count,platelet count,and heart rate.For DNA methylation association analysis,we find that two CpGs(cg16687447,cg06947206)upstream of PTEN were associated with platelet count.In conclusion,extreme hypoxia exposure leads to epigenetic modifications and phenotypic alterations of TEA,providing us clues for exploring the molecular mechanism underlying changes under extreme hypoxia conditions.
