Spaceflight and the Differential Gene Expression of Human Stem Cell-Derived Cardiomyocytes

Abstract

The National Aeronautics and Space Administration (NASA) has performed many experiments on the International Space Station (ISS) to further understand how conditions in space can affect life on Earth. This project analyzed GLDS-258, a gene set from NASA’s GeneLab repository which examines the impact of microgravity on human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). While many datasets have been run through NASA’s RNA-Seq Consensus Pipeline (RCP) to study differential gene expression in space, a Homo sapiens dataset has yet to be analyzed using the RCP. The aim of this project was to run the first Homo sapiens dataset, GLDS-258, through the RCP on the San Jose State University College of Engineering High Performance Computing Cluster and investigate any biological significance from the results. In this study, a total of 18 hiPSC-CMs samples from ground control, flight, and post- flight groups are run through the RPC. The resulting differential gene expression data was further analyzed for biological significance using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA). Results showed that most genes were differentially expressed in ground control versus flight groups, while post- flight groups and ground control groups did not have as many differentially expressed genes. Gene set analysis showed significant expression of genes in mitochondrial pathways as well as genes related to neurodegenerative diseases such as Alzheimer’s, Huntington’s, and Parkinson’s disease. These results indicate that exposure to microgravity may play a role in altering expression of genes which are related to neurodegenerative pathways in cardiac cells. Our results demonstrate that it is possible to process Homo sapiens data through the RPC, and suggest that cardiomyocytes exposed to microgravity may exacerbate neurodegenerative disease progression.