Abstract：
BACKGROUND: Schizophrenia is a mental disorder that causes considerable morbidity, whose risk largely results from genetic factors. Setd1a is a gene implicated in schizophrenia.
OBJECTIVE: To study the gene expression changes found in heterozygous Setd1a± knockout mice in order to gain useful insight into schizophrenia pathogenesis.
METHODS: We mined a single-cell RNA sequencing (scRNAseq) dataset from the prefrontal cortex (PFC) and striatum of Setd1a± mice and identified cell type-specific differentially expressed genes (DEGs) and differential transcript usage (DTU). DEGs and genes containing DTU found in each cell type were used to identify affected biological pathways using Ingenuity Pathway Analysis (IPA).
RESULTS: We 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.
CONCLUSIONS: Processes 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.
OBJECTIVE: To study the gene expression changes found in heterozygous Setd1a± knockout mice in order to gain useful insight into schizophrenia pathogenesis.
METHODS: We mined a single-cell RNA sequencing (scRNAseq) dataset from the prefrontal cortex (PFC) and striatum of Setd1a± mice and identified cell type-specific differentially expressed genes (DEGs) and differential transcript usage (DTU). DEGs and genes containing DTU found in each cell type were used to identify affected biological pathways using Ingenuity Pathway Analysis (IPA).
RESULTS: We 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.
CONCLUSIONS: Processes 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.
摘要：
背景：精神分裂症是一种导致相当发病率的精神障碍，其风险主要来自遗传因素。Sett1a是与精神分裂症有关的基因。
目的：研究在杂合子Setd1a±敲除小鼠中发现的基因表达变化，以获得对精神分裂症发病机制的有用见解。
方法：我们从Setd1a±小鼠的前额叶皮质（PFC）和纹状体中挖掘了单细胞RNA测序（scRNAseq）数据集，并鉴定了细胞类型特异性差异表达基因（DEG）和差异转录物使用（DTU）。在每种细胞类型中发现的DEGs和含有DTU的基因用于使用创造性途径分析(IPA)鉴定受影响的生物学途径。
结果：我们在PFC中的所有细胞类型中鉴定了273个独特的DEGs和含有DTU的675个独特的基因峰。在纹状体中，我们在所有细胞类型中鉴定出327个独特的DEGs和8个含有DTU的独特基因峰.从PFC和纹状体中发现的DEGs分析中的关键IPA发现涉及蛋白质合成的过程，线粒体功能，细胞代谢，和炎症。PFC中含有DTU的基因的IPA分析指向蛋白质合成，以及涉及细胞内信号传导和神经传递的细胞活动。一个典型的途径，\'EIF2信令\',参与蛋白质合成的调节，在PFCDEG中检测到，纹状体DEGs,和含有DTU的PFC基因，提请注意其在精神分裂症病理生理学中的重要性。
结论：一般涉及蛋白质合成的过程，特别是“EIF2信号通路”可能成为精神分裂症新研究策略和生物标志物开发的目标。
目的：研究在杂合子Setd1a±敲除小鼠中发现的基因表达变化，以获得对精神分裂症发病机制的有用见解。
方法：我们从Setd1a±小鼠的前额叶皮质（PFC）和纹状体中挖掘了单细胞RNA测序（scRNAseq）数据集，并鉴定了细胞类型特异性差异表达基因（DEG）和差异转录物使用（DTU）。在每种细胞类型中发现的DEGs和含有DTU的基因用于使用创造性途径分析(IPA)鉴定受影响的生物学途径。
结果：我们在PFC中的所有细胞类型中鉴定了273个独特的DEGs和含有DTU的675个独特的基因峰。在纹状体中，我们在所有细胞类型中鉴定出327个独特的DEGs和8个含有DTU的独特基因峰.从PFC和纹状体中发现的DEGs分析中的关键IPA发现涉及蛋白质合成的过程，线粒体功能，细胞代谢，和炎症。PFC中含有DTU的基因的IPA分析指向蛋白质合成，以及涉及细胞内信号传导和神经传递的细胞活动。一个典型的途径，\'EIF2信令\',参与蛋白质合成的调节，在PFCDEG中检测到，纹状体DEGs,和含有DTU的PFC基因，提请注意其在精神分裂症病理生理学中的重要性。
结论：一般涉及蛋白质合成的过程，特别是“EIF2信号通路”可能成为精神分裂症新研究策略和生物标志物开发的目标。
