Jonathan Schisler is senior co-author on two collaborative papers with the Afshin Beheshti lab and others published in Cell and Cell Reports a week apart detailing the results of NASA space flight studies.
Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact
CELL | VOLUME 183, ISSUE 5, P1185-1201.E20, NOVEMBER 25, 2020
Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, we used a multi-omics, systems biology analytical approach using biomedical profiles from fifty-nine astronauts and data from NASA’s GeneLab derived from hundreds of samples flown in space to determine transcriptomic, proteomic, metabolomic, and epigenetic responses to spaceflight. Overall pathway analyses on the multi-omics datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions. Importantly, NASA’s Twin Study provided a platform to confirm several of our principal findings. Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight.
Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development
CELL REPORTS | VOLUME 33, ISSUE 10, 108448, DECEMBER 08, 2020
Open Access Published:November 25, 2020 DOI:https://doi.org/10.1016/j.celrep.2020.108448
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.
Cover of Cell
Image: Cover of Cell in Nov 25, 2020 issue that features a review (Afshinnekoo et al., 2020) and a research article (da Silveira et al., 2020) as part of a special collection of papers on “The Biology of Spaceflight” published across Cell Press. The cover art shows city lights spanning Japan at night, glimmering below Earth’s thin atmosphere, as well as the International Space Station with a docked Soyuz Space Capsule (top). Photograph by Scott Kelly.