Numerous alternative splicing (AS) events have been documented in Alzheimer's disease (AD). However, cell type-specific AS analysis is still lacking. We described AS events in the hippocampal microglia sorted by CD45 and CD11b from Aβ precursor protein (APP) and non-transgenic (Ntg) mice. GSE171195 dataset was downloaded from GEO database, aligned to GRCm39 genome. Skipped exon (SE), alternative 3’SS (A3SS), retained intron (RI), alternative 5’SS (A5SS), and mutually exclusive exons (MXE) were evaluated using rMATS and maser. Differential expressed genes or transcripts were analyzed via limma. Gene ontology and correlation analyses were performed with clusterProfiler and ggcorrplot R packages. 36,340 raw counts of AS were identified, and 95 significant AS events were eventually selected with strict criteria: (1) average coverage >5; (2) delta percent spliced in >0.1. SE was the most common AS events (68.42%), followed by A3SS and RI. Autophagy genes were mainly spliced in SE events, actin depolymerization genes spliced in A3SS events, while synaptic plasticity related genes were mainly spliced in RI pattern. These significant AS events may be regulated by dysregulated splicing factors in AD. In conclusion, we revealed microglia specific AS events in AD, and our study provides novel pathological mechanisms in the pathogenesis of AD.

中文翻译：

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阿尔茨海默病中不同的小胶质细胞选择性剪接

在阿尔茨海默病 (AD) 中记录了许多选择性剪接 (AS) 事件。然而，仍然缺乏特定于细胞类型的 AS 分析。我们描述了通过 Aβ 前体蛋白 (APP) 和非转基因 (Ntg) 小鼠的 CD45 和 CD11b 分类的海马小胶质细胞中的 AS 事件。GSE171195 数据集是从 GEO 数据库下载的，与 GRCm39 基因组对齐。跳过外显子 (SE)、替代 3'SS (A3SS)、保留内含子 (RI)、替代 5'SS (A5SS) 和互斥外显子 (MXE) 使用 rMATS 和 maser 进行评估。通过 limma 分析差异表达的基因或转录物。使用 clusterProfiler 和 ggcorrplot R 包进行基因本体论和相关性分析。确定了 36,340 个 AS 原始计数，并最终选择了 95 个重要的 AS 事件，标准严格：（1）平均覆盖率>5；(2) 增量百分比拼接 >0.1。SE 是最常见的 AS 事件 (68.42%)，其次是 A3SS 和 RI。自噬基因主要拼接在SE事件中，肌动蛋白解聚基因主要拼接在A3SS事件中，而突触可塑性相关基因主要拼接在RI模式中。这些重要的 AS 事件可能受到 AD 中失调的剪接因子的调节。总之，我们揭示了 AD 中小胶质细胞特异性 AS 事件，我们的研究提供了 AD 发病机制中的新病理机制。这些重要的 AS 事件可能受到 AD 中失调的剪接因子的调节。总之，我们揭示了 AD 中小胶质细胞特异性 AS 事件，我们的研究提供了 AD 发病机制中的新病理机制。这些重要的 AS 事件可能受到 AD 中失调的剪接因子的调节。总之，我们揭示了 AD 中小胶质细胞特异性 AS 事件，我们的研究提供了 AD 发病机制中的新病理机制。