Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development.
Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development.
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DOI：
10.1016/j.celrep.2020.108448
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发表时间：
2020-12-08
期刊：
影响因子：
8.8
通讯作者：
Beheshti A
中科院分区：
文献类型：
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作者：
Malkani S;Chin CR;Cekanaviciute E;Mortreux M;Okinula H;Tarbier M;Schreurs AS;Shirazi-Fard Y;Tahimic CGT;Rodriguez DN;Sexton BS;Butler D;Verma A;Bezdan D;Durmaz C;MacKay M;Melnick A;Meydan C;Li S;Garrett-Bakelman F;Fromm B;Afshinnekoo E;Langhorst BW;Dimalanta ET;Cheng-Campbell M;Blaber E;Schisler JC;Vanderburg C;Friedländer MR;McDonald JT;Costes SV;Rutkove S;Grabham P;Mason CE;Beheshti A
我们已经确定并验证了一种与航天飞行相关的微小核糖核酸（miRNA）特征，该特征在啮齿动物和人类对模拟的短期和长期航天飞行做出反应时是相同的。先前的研究已经确定了调节啮齿动物对近地轨道航天飞行反应的miRNA，并且我们已经证实了这些提出的与航天飞行相关的miRNA在对模拟航天飞行条件做出反应的啮齿动物中的表达。此外，美国国家航空航天局（NASA）双胞胎研究中的宇航员样本在miRNA测序、单细胞RNA测序（scRNA - seq）以及转座酶可接近染色质的单细胞分析（scATAC - seq）数据中证实了这些表达特征。另外，发现这些miRNA的一个子集（miR - 125、miR - 16和let - 7a）可调节模拟深空辐射造成的血管损伤。为了证明关键的与航天飞行相关的miRNA的生理相关性，我们利用拮抗剂抑制它们的表达，并成功挽救了人类3D血管构建体中模拟的深空辐射介导的损伤。
马尔卡尼等人揭示了循环微小核糖核酸的作用，它既是与航天飞行相关的健康风险的潜在生物标志物，也是减轻太空环境对身体造成损害的一种对策。
We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated, short-duration and long-duration spaceflight. Previous studies have identified miRNAs that regulate rodent responses to spaceflight in low-Earth orbit, and we have confirmed the expression of these proposed spaceflight-associated miRNAs in rodents reacting to simulated spaceflight conditions. Moreover, astronaut samples from the NASA Twins Study confirmed these expression signatures in miRNA sequencing, single-cell RNA sequencing (scRNA-seq), and single-cell assay for transposase accessible chromatin (scATAC-seq) data. Additionally, a subset of these miRNAs (miR-125, miR-16, and let-7a) was found to regulate vascular damage caused by simulated deep space radiation. To demonstrate the physiological relevance of key spaceflight-associated miRNAs, we utilized antagomirs to inhibit their expression and successfully rescue simulated deep-space-radiation-mediated damage in human 3D vascular constructs. Malkani et al. uncover the role of circulating microRNAs as both a potential biomarker for health risks associated with spaceflight and a countermeasure to mitigate the damage caused to the body by the space environment.