J Sebastian Garcia-Medina, Karolina Sienkiewicz, S Anand Narayanan, Eliah G Overbey, Kirill Grigorev, Krista A Ryon, Marissa Burke, Jacqueline Proszynski, Braden Tierney, Caleb M Schmidt, Nuria Mencia-Trinchant, Remi Klotz, Veronica Ortiz, Jonathan Foox, Christopher Chin, Deena Najjar, Irina Matei, Irenaeus Chan, Carlos Cruchaga, Ashley Kleinman, JangKeun Kim, Alexander Lucaci, Conor Loy, Omary Mzava, Iwijn De Vlaminck, Anvita Singaraju, Lynn E Taylor, Julian C Schmidt, Michael A Schmidt, Kelly Blease, Juan Moreno, Andrew Boddicker, Junhua Zhao, Bryan Lajoie, Andrew Altomare, Semyon Kruglyak, Shawn Levy, Min Yu, Duane C Hassane, Susan M Bailey, Kelly Bolton, Jaime Mateus, Christopher E Mason
{"title":"基因组和克隆造血的稳定性与短时太空飞行期间免疫、cfDNA、线粒体和端粒长度的变化形成鲜明对比。","authors":"J Sebastian Garcia-Medina, Karolina Sienkiewicz, S Anand Narayanan, Eliah G Overbey, Kirill Grigorev, Krista A Ryon, Marissa Burke, Jacqueline Proszynski, Braden Tierney, Caleb M Schmidt, Nuria Mencia-Trinchant, Remi Klotz, Veronica Ortiz, Jonathan Foox, Christopher Chin, Deena Najjar, Irina Matei, Irenaeus Chan, Carlos Cruchaga, Ashley Kleinman, JangKeun Kim, Alexander Lucaci, Conor Loy, Omary Mzava, Iwijn De Vlaminck, Anvita Singaraju, Lynn E Taylor, Julian C Schmidt, Michael A Schmidt, Kelly Blease, Juan Moreno, Andrew Boddicker, Junhua Zhao, Bryan Lajoie, Andrew Altomare, Semyon Kruglyak, Shawn Levy, Min Yu, Duane C Hassane, Susan M Bailey, Kelly Bolton, Jaime Mateus, Christopher E Mason","doi":"10.1093/pcmedi/pbae007","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Result: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11022651/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight.\",\"authors\":\"J Sebastian Garcia-Medina, Karolina Sienkiewicz, S Anand Narayanan, Eliah G Overbey, Kirill Grigorev, Krista A Ryon, Marissa Burke, Jacqueline Proszynski, Braden Tierney, Caleb M Schmidt, Nuria Mencia-Trinchant, Remi Klotz, Veronica Ortiz, Jonathan Foox, Christopher Chin, Deena Najjar, Irina Matei, Irenaeus Chan, Carlos Cruchaga, Ashley Kleinman, JangKeun Kim, Alexander Lucaci, Conor Loy, Omary Mzava, Iwijn De Vlaminck, Anvita Singaraju, Lynn E Taylor, Julian C Schmidt, Michael A Schmidt, Kelly Blease, Juan Moreno, Andrew Boddicker, Junhua Zhao, Bryan Lajoie, Andrew Altomare, Semyon Kruglyak, Shawn Levy, Min Yu, Duane C Hassane, Susan M Bailey, Kelly Bolton, Jaime Mateus, Christopher E Mason\",\"doi\":\"10.1093/pcmedi/pbae007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Result: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":33608,\"journal\":{\"name\":\"Precision Clinical Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-04-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11022651/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Precision Clinical Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/pcmedi/pbae007\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Precision Clinical Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/pcmedi/pbae007","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight.
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.
期刊介绍:
Precision Clinical Medicine (PCM) is an international, peer-reviewed, open access journal that provides timely publication of original research articles, case reports, reviews, editorials, and perspectives across the spectrum of precision medicine. The journal's mission is to deliver new theories, methods, and evidence that enhance disease diagnosis, treatment, prevention, and prognosis, thereby establishing a vital communication platform for clinicians and researchers that has the potential to transform medical practice. PCM encompasses all facets of precision medicine, which involves personalized approaches to diagnosis, treatment, and prevention, tailored to individual patients or patient subgroups based on their unique genetic, phenotypic, or psychosocial profiles. The clinical conditions addressed by the journal include a wide range of areas such as cancer, infectious diseases, inherited diseases, complex diseases, and rare diseases.