Longitudinal transcriptomic and epigenetic analysis in astronauts reveals dynamic immune response to spaceflight

Abstract

Abstract With the advance of the space industry, the number of astronauts is increasing exponentially. A better understanding of the molecular changes in astronauts in response to spaceflight is required. Here we studied the transcriptomic and epigenetic changes that are subjected to spaceflight. We analyzed the blood samples of two astronauts collected at three timepoints of two weeks before (T0), twenty-four hours after (T2) and three months after (T3) spaceflight. We found monocytes were downregulated at T2 after the spaceflight and reversed to baseline T0 after three months of post-spaceflight at T3. Transcriptomic analysis identified two groups of genes that showed distinct expression patterns, one with transient up-regulation of the expression immediately after spaceflight and another one with transient down-regulation. Pathway analysis of the two groups revealed that protein modification pathway and cell cycle pathway were enriched, possibly supporting the conversion of monocytes to macrophages via autophagy. Epigenetic analysis identified four methylation patterns that showed transient and persistent changes, enriched in the nervous system development pathway and cell apoptosis pathway. Region-level methylation responses point to the genes involved in bone diseases, such as FBLIM1, IHH, and SCAMP2. eQTM analysis suggested a link between RNA transcriptional activity and DNA methylation through transcriptional regulator ZNF684. In conclusion, our longitudinal transcriptomic and epigenetic analysis in astronauts provides a comprehensive view of the physiological impact of spaceflight on human biology that potentially has systemic large short-term and smaller long-term effects on bodily functions.