Multi-omic, Single-Cell, and Biochemical Profiles of Astronauts Guide Pharmacological Strategies for Returning to Gravity.
Multi-omic, Single-Cell, and Biochemical Profiles of Astronauts Guide Pharmacological Strategies for Returning to Gravity.
复制标题
DOI：
10.1016/j.celrep.2020.108429
复制
发表时间：
2020-12-08
期刊：
影响因子：
8.8
通讯作者：
Mason, Christopher E.
中科院分区：
文献类型：
--
作者：
Gertz, Monica L.;Chin, Christopher R.;Tomoiaga, Delia;MacKay, Matthew;Chang, Christina;Butler, Daniel;Afshinnekoo, Ebrahim;Bezdan, Daniela;Schmidt, Michael A.;Mozsary, Christopher;Melnick, Ari;Garrett-Bakelman, Francine;Crucian, Brian;Lee, Stuart M. C.;Zwart, Sara R.;Smith, Scott M.;Meydan, Cem;Mason, Christopher E.
美国国家航空航天局（NASA）的双胞胎研究在NASA首次为期1年的国际空间站（ISS）任务期间创建了一名宇航员的综合分子图谱，并与地球上的同卵双胞胎进行了比较。在如此长时间的任务后返回地球时观察到的独特生化特征（例如，白细胞介素 - 1[IL - 1]/6/10、C - 反应蛋白[CRP]、C - C基序趋化因子配体2[CCL2]、IL - 1受体拮抗剂[IL - 1ra]和肿瘤坏死因子α[TNF - α]的峰值）引发了有关人体对重力的反应以及如何为未来宇航员做规划的新问题，特别是关于炎症的引发或消退方面。在此，对外周血单个核细胞（PBMCs）进行的单细胞、多组学（100重表位图谱和基因表达）分析显示，飞行后血细胞组成和基因表达发生了变化，特别是单核细胞和树突状细胞前体。这些变化与飞行引起的细胞因子和免疫系统应激一致，随后是对重力作出反应的骨骼肌再生。最后，我们参照其他28名宇航员6个月的任务检查了这些图谱，并详细阐述了未来任务中返回重力环境时可能采取的药物干预措施。
格茨等人对NASA双胞胎研究的着陆数据进行了重新分析，表明生化特征反映的是萎缩后肌肉的再生，而非有害的炎症反应。这是通过肌肉来源的IL - 6抗炎级联反应介导的。单细胞分析支持这一作用。还讨论了潜在的药物干预措施。
The National Aeronautics and Space Administration (NASA) Twins Study created an integrative molecular profile of an astronaut during NASA’s first 1-year mission on the International Space Station (ISS) and included comparisons to an identical Earth-bound twin. The unique biochemical profiles observed when landing on Earth after such a long mission (e.g., spikes in interleukin-1 [IL-1]/6/10, c-reactive protein [CRP], C-C motif chemokine ligand 2 [CCL2], IL-1 receptor antagonist [IL-1ra], and tumor necrosis factor alpha [TNF-α]) opened new questions about the human body’s response to gravity and how to plan for future astronauts, particularly around initiation or resolution of inflammation. Here, single-cell, multi-omic (100-plex epitope profile and gene expression) profiling of peripheral blood mononuclear cells (PBMCs) showed changes to blood cell composition and gene expression post-flight, specifically for monocytes and dendritic cell precursors. These were consistent with flight-induced cytokine and immune system stress, followed by skeletal muscle regeneration in response to gravity. Finally, we examined these profiles relative to 6-month missions in 28 other astronauts and detail potential pharmacological interventions for returning to gravity in future missions. Gertz et al. present a re-analysis of the landing data from the NASA Twins Study, suggesting that the biochemical signature reflects muscle regeneration after atrophy rather than a detrimental inflammatory response. This is mediated through muscle-derived IL-6 anti-inflammatory cascades. Single-cell analysis supports this role. Potential pharmacological interventions are also discussed.
登录
查看更多内容
影响因子：
8.1
作者：
Charoenlarp P;Rajendran AK;Iseki S
通讯作者：
Iseki S
DOI：
10.1097/00005768-200010000-00013
发表时间：
2000-10-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Akima, H;Kawakami, Y;Fukunaga, T
通讯作者：
Fukunaga, T
影响因子：
64.8
作者：
GORDON, JR;GALLI, SJ
通讯作者：
GALLI, SJ
影响因子：
4.4
作者：
Lauw, FN;Pajkrt, D;van der Poll, T
通讯作者：
van der Poll, T
影响因子：
3.6
作者：
Kim, Jiyoung;Kim, Na Kyeong;Choi, Byung Hyune
通讯作者：
Choi, Byung Hyune