Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development
Sherina Malkani, Christopher R. Chin, Egle Cekanaviciute, Marie Mortreux, Hazeem Okinula, Marcel Tarbier, Ann‐Sofie Schreurs, Yasaman Shirazi‐Fard, Candice Tahimic, Deyra N. Rodríguez, Brittany S. Sexton, Daniel Butler, Akanksha Verma, Daniela Bezdan, Ceyda Durmaz, Matthew MacKay, Ari Melnick, Cem Meydan, Sheng Li, Francine E. Garrett-Bakelman, Bastian Fromm, Ebrahim Afshinnekoo, Bradley W. Langhorst, Eileen T. Dimalanta, Margareth Cheng-Campbell, Elizabeth A. Blaber, Jonathan C. Schisler, Charles Vanderburg, Marc R. Friedländer, J. Tyson McDonald, Sylvain V. Costes, Seward B. Rutkove, Peter Grabham, Christopher E. Mason, Afshin Beheshti
Abstract
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.