MicroRNA Microarray Analysis of Human-Induced Pluripotent Stem Cell-Derived Neurons and Cardiomyocytes following Exposure to the Organophosphate Nerve Agents Soman and VX
Abstract
Chemical warfare nerve agents (CWNAs) are potent cholinesterase inhibitors that may also have non-cholinesterase effects. Several in vivo studies have shown that exposure to CWNA compounds induces damage in the brain and heart. Underlying mechanisms of this damage are a critical area of research for the development of medical countermeasures. This study utilized microRNA (miRNA) analysis to evaluate potential direct cellular effects of the nerve agents GD (soman; O-Pinacolyl methylphosphonofluoridate) or VX (o-ethyl-s-[2 (diisopropylamino) ethyl]) on neurons derived from human-induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes. This approach was taken since miRNA expression changes are stimulus specific and no previous studies of miRNA profiles have been conducted for CWNA exposure. Cells were exposed to GD or VX at concentrations of 0 micro M, 0.1 micro M or 100 micro M for either 1 hour or 6 hours. Following exposure, isolated total RNA was processed for miRNA microarray analysis and analyzed for significant changes. GD- and VX-treated samples were analyzed separately. Changes in miRNA expression for both neurons and cardiomyocytes were modest. Nonetheless, expression profiles that were unique to either GD or VX exposure were observed with both neurons and cardiomyocytes. Further analysis of select miRNAs, namely, neuronal miR-941 and cardiomyocyte miR-576-3p, supports this observation that expression changes are dependent on the nerve agent.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 10, 2020
- Accession Number
- AD1108972
Entities
People
- E. K Yego
- Heidi M. Hoard-fruchey
- James F Iii Dillman
Organizations
- United States Army Medical Research Institute of Chemical Defense