Spaceflight-Associated Changes of snoRNAs in Peripheral Blood Mononuclear Cells and Plasma Exosomes-A Pilot Study.
Spaceflight-Associated Changes of snoRNAs in Peripheral Blood Mononuclear Cells and Plasma Exosomes-A Pilot Study.
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DOI：
10.3389/fcvm.2022.886689
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发表时间：
2022
影响因子：
3.6
通讯作者：
Garikipati, Venkata Naga Srikanth
中科院分区：
文献类型：
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作者：
Rai, Amit Kumar;Rajan, K. Shanmugha;Bisserier, Malik;Brojakowska, Agnieszka;Sebastian, Aimy;Evans, Angela C.;Coleman, Matthew A.;Mills, Paul J.;Arakelyan, Arsen;Uchida, Shizuka;Hadri, Lahouaria;Goukassian, David A.;Garikipati, Venkata Naga Srikanth
在航天飞行期间，宇航员受到各种生理和心理压力，这些压力与不利的健康影响有关。因此，开发新型诊断工具来预测宇航员健康状况的早期变化的需求尚未得到满足。小核仁RNA（snoRNA）是一类短的非编码RNA（60-300个核苷酸），已知其引导核糖体RNA（rRNA）、小核RNA（snRNA）或信使RNA（mRNA）的2′-O-甲基化（Nm）或假尿苷（pseudouridine）。新出现的证据表明，失调的snoRNA可能是调节基本细胞机制以及癌症、心脏病和神经系统疾病发病机制的关键参与者。因此，我们试图确定航天飞行诱导的snoRNA是否在宇航员外周血（PB）血浆细胞外囊泡（PB-EV）和外周血单核细胞（PBMC）中发生变化。使用无偏小RNA测序（sRNAseq），我们评估了从1998年至2001年期间进行了为期12天的航天飞机任务的宇航员（n = 5/组）中分离的PB-EV snoRNA含量的变化。使用严格的截止值（倍数变化> 2或log 2-倍数变化>1，FDR < 0.05），与发射前10天（L-10）相比，我们在返回后3天（R + 3）在PB-EV中检测到21个下调和9个上调的snoRNA。qPCR验证显示，与L-10相比，SNORA 74 A在R + 3处显著下调。接下来，我们测定了R + 3和L-10时宇航员PBMC中snoRNA的表达水平（n = 6/组）。qPCR分析进一步证实，与L-10相比，R + 3时宇航员PBMC中的SNORA 19和SNORA 47显著增加。值得注意的是，许多下调的snoRNA引导的rRNA修饰，包括四个NMS和五个NMSs。我们的研究结果表明，航天引起PB-EV和PBMCs snoRNA表达的变化，从而表明snoRNA可能作为监测宇航员健康的潜在新生物标志物。
During spaceflight, astronauts are exposed to various physiological and psychological stressors that have been associated with adverse health effects. Therefore, there is an unmet need to develop novel diagnostic tools to predict early alterations in astronauts’ health. Small nucleolar RNA (snoRNA) is a type of short non-coding RNA (60–300 nucleotides) known to guide 2′-O-methylation (Nm) or pseudouridine (ψ) of ribosomal RNA (rRNA), small nuclear RNA (snRNA), or messenger RNA (mRNA). Emerging evidence suggests that dysregulated snoRNAs may be key players in regulating fundamental cellular mechanisms and in the pathogenesis of cancer, heart, and neurological disease. Therefore, we sought to determine whether the spaceflight-induced snoRNA changes in astronaut’s peripheral blood (PB) plasma extracellular vesicles (PB-EV) and peripheral blood mononuclear cells (PBMCs). Using unbiased small RNA sequencing (sRNAseq), we evaluated changes in PB-EV snoRNA content isolated from astronauts (n = 5/group) who underwent median 12-day long Shuttle missions between 1998 and 2001. Using stringent cutoff (fold change > 2 or log2-fold change >1, FDR < 0.05), we detected 21 down-and 9—up-regulated snoRNAs in PB-EVs 3 days after return (R + 3) compared to 10 days before launch (L-10). qPCR validation revealed that SNORA74A was significantly down-regulated at R + 3 compared to L-10. We next determined snoRNA expression levels in astronauts’ PBMCs at R + 3 and L-10 (n = 6/group). qPCR analysis further confirmed a significant increase in SNORA19 and SNORA47 in astronauts’ PBMCs at R + 3 compared to L-10. Notably, many downregulated snoRNA-guided rRNA modifications, including four Nms and five ψs. Our findings revealed that spaceflight induced changes in PB-EV and PBMCs snoRNA expression, thus suggesting snoRNAs may serve as potential novel biomarkers for monitoring astronauts’ health.
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细胞外囊泡以及系统生物学和计算建模在心脏修复中的应用。
影响因子：
20.1
作者：
Garikipati VNS;Shoja-Taheri F;Davis ME;Kishore R
通讯作者：
Kishore R
影响因子：
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作者：
Ding Y;Sun Z;Zhang S;Li Y;Han X;Xu Q;Zhou L;Xu H;Bai Y;Xu C;Ding H;Ge Y;Wang W
通讯作者：
Wang W
影响因子：
4
作者：
James V;Nizamudeen ZA;Lea D;Dottorini T;Holmes TL;Johnson BB;Arkill KP;Denning C;Smith JGW
通讯作者：
Smith JGW
影响因子：
4.6
作者：
Chikne V;Doniger T;Rajan KS;Bartok O;Eliaz D;Cohen-Chalamish S;Tschudi C;Unger R;Hashem Y;Kadener S;Michaeli S
通讯作者：
Michaeli S
影响因子：
5.4
作者：
Bisserier M;Shanmughapriya S;Rai AK;Gonzalez C;Brojakowska A;Garikipati VNS;Madesh M;Mills PJ;Walsh K;Arakelyan A;Kishore R;Hadri L;Goukassian DA
通讯作者：
Goukassian DA