Single-Cell Analysis Identifies Conserved Features of Immune Dysfunction in Simulated Microgravity and Spaceflight

With the renewed interest in space exploration, there is a significant need to understand how biological processes are affected by exposure to microgravity environments.  Several studies have shown that immune function is impaired due to microgravity, but the mechanisms and signaling pathways involved are not well understood.  Recently, Wu et al. utilized microgravity simulators on human PBMCs and performed an array of single-cell analysis studies to better understand the mechanisms that contribute to this impaired immunity.  The group identified 28 different immune cell clusters that showed measurable differences in cells that were exposed to microgravity relative to control gravity cells.  Additionally, they found 375 core, differentially expressed genes between the two groups; these proteins were present in several different pathways, including RhoA signaling, sirtuin signaling, oxidative stress, fibrosis signaling, actin-based motility, and several others. The group determined that the microgravity-exposed groups had a significantly higher “inflammatory aging” and a higher rate of latent pathogen activation.  Agonist activation also produced differential gene expression in cells exposed to microgravity relative to control gravity cells and also showed several of the same key pathways were affected. The group then compared their 375 core genes to datasets from studies on people and mice flow on the international space station. Of note, they found measurable overlap in these studies and found that pathways affecting the cytoskeleton were consistently altered.  The group measured changes in actin morphology and confirmed that these changes were related to enhanced activation of Cdc42.  Collectively, this expansive study identified several pathways and processes that may be contributing to immune dysfunction.  Cytoskeleton Inc.’s G-LISA activation assays including the Cde42 G-LISA (Cat. # BK127), Rac1 G-LISA (Cat. # BK128), and the RhoA G-LISA (Cat. # BK124) were used throughout this study to analyze the activation status of these small GTPases.