Analysis of single-cell transcriptome data from a mouse model implicates protein synthesis dysfunction in schizophrenia.

backgroundSchizophrenia is a mental disorder that causes considerable morbidity, whose risk largely results from genetic factors. Setd1a is a gene implicated in schizophrenia.

objectiveTo study the gene expression changes found in heterozygous Setd1a

methodsWe mined a single-cell RNA sequencing (scRNAseq) dataset from the prefrontal cortex (PFC) and striatum of Setd1a

resultsWe identified 273 unique DEGs across all cell types in PFC and 675 unique gene peaks containing DTU. In striatum, we identified 327 unique DEGs across all cell types and 8 unique gene peaks containing DTU. Key IPA findings from the analysis of DEGs found in PFC and striatum implicate processes involved in protein synthesis, mitochondrial function, cell metabolism, and inflammation. IPA analysis of genes containing DTU in PFC points to protein synthesis, as well as cellular activities involving intracellular signaling and neurotransmission. One canonical pathway, 'EIF2 Signaling', which is involved in the regulation of protein synthesis, was detected in PFC DEGs, striatum DEGs, and PFC genes containing DTU, drawing attention to its importance in schizophrenia pathophysiology.

conclusionProcesses involving protein synthesis in general and the 'EIF2 Signaling' pathway in particular could be targets for the development of new research strategies and biomarkers in schizophrenia.