Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic approach.Despite advances,there remains mu...Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic approach.Despite advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation exposure.Methods To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA extraction.Telomere length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational burden.Result Telomere elongation occurred during spaceflight and shortened after return to Earth.Cell-free DNA analysis revealed increased immune cell signatures post-flight.No significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was observed.The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.Conclusion Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth.CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career astronauts.This study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.展开更多
基金supported by the Leukemia and Lymphoma Society (Grants No.LLS 9238-16 and MCL7001-18)the National Institutes of Health (Grants No.P01CA214274,R01CA249054 and R01MH117406)the WorldQuant Foundation,NASA (Grants No.80NSSC19K0432,80NSSC22K0254,NNH18ZTT001N-FG2,NNX13AE45G,NNX14AH50G,NNX17AB26G).
文摘Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic approach.Despite advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation exposure.Methods To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA extraction.Telomere length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational burden.Result Telomere elongation occurred during spaceflight and shortened after return to Earth.Cell-free DNA analysis revealed increased immune cell signatures post-flight.No significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was observed.The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.Conclusion Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth.CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career astronauts.This study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.
