The Role of H2AC21 and H2AC11 in Reducing Thymic Epithelial Cell Proliferation

Thymic involution is a stress- and age-induced phenomenon that diminishes the rate of naive T cell development and impairs immune system function. It is also hypothesized to be expedited during spaceflight due to elevated oxidative stress. In conjunction with increased pathogenicity of bacteria in microgravity, accelerated thymic involution may present additional health risks to astronauts as NASA pursues human spaceflight outside of Low Earth Orbit (LEO). We analyzed the impacts of spaceflight on gene expression in the mouse thymus using the GeneLab Galaxy platform and transcriptomics data from the GLDS-289 study titled: “Impact of Spaceflight on Gene Expression in the Thymus”. This study investigated thymic atrophy in three groups of mice: spaceflight, artificial gravity during spaceflight, and ground controls. Our analysis of differentially expressed genes and involved pathways, using Gene Set Enrichment Analysis and volcano plots, indicated a downregulation of histone genes H2AC11 and H2AC21 as well as cyclin genes CDK1 and CDC25 in the spaceflight group relative to ground controls. We hypothesize that decreased expression of these genes leads to reduced thymic epithelial cell proliferation and decreased T cell maturation. We developed a proposal for a series of experiments to test our hypothesis; RNA sequencing and Western blot analyses will be used to examine the relationship between thymic involution and these four genes as they are silenced in developing mouse thymic organoids. Our proposal thus serves as a first step towards advancing our understanding of the impacts of microgravity on thymic cell proliferation and maturation, and more broadly, adaptive immune system functions in space with the goal to support astronaut and terrestrial health.