Exploratory longitudinal analysis of a PIN1-associated gene panel in PBMCs during orbital spaceflight

Abstract

Spaceflight exposes astronauts to a combination of microgravity, radiation, circadian disruption, isolation, and operational stress that may influence immune and transcriptional regulation. In this exploratory study, we examined peripheral blood mononuclear cell RNA-sequencing data from three Axiom-3 astronauts sampled before launch (L−7) and on International Space Station Days 4, 7, and 10. A separate Galactic-07 participant sampled before launch and 3 h after suborbital flight was included for descriptive context only. The analysis focused on a preselected panel comprising PIN1 and ten biologically associated genes involved in cell-cycle regulation, stress responses, transcriptional control, innate immunity, and oxidative responses. Participant-adjusted longitudinal analysis identified significant overall time-associated variation in PIN1, TP53, PML, MYC, NCF1, NCF2, IRF3, POLR2A, and SFN after Benjamini–Hochberg correction. Several additional genes exhibited descriptive downward expression patterns without meeting the adjusted significance threshold. Because the cohort was small and the measurements were limited to bulk-PBMC mRNA abundance, the findings do not establish altered PIN1 protein activity, a mission-specific regulatory network, or biomarker performance. Instead, they provide hypothesis-generating evidence supporting further evaluation of PIN1-associated transcriptional responses in larger astronaut cohorts using protein-level, functional, and cell-type-resolved analyses.