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
Cell Reports 33 (10) 108448 [2020-12-08; online 2020-11-25]
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.