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pmid:36006403

Distinct microglia alternative splicing in Alzheimer's disease.

Yanjun Lu · Lu Tan · Jiazhao Xie · Liming Cheng · Xiong Wang

Aging · 2022 doi:10.18632/aging.204223

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
Distinct microglia alternative splicing in Alzheimer's disease.
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10.18632/aging.204223
pmid
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[0]
Yanjun Lu
[1]
Lu Tan
[2]
Jiazhao Xie
[3]
Liming Cheng
[4]
Xiong Wang
journal
Aging
year
2022
abstract
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.
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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.
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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.
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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.
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Gas6 improves plaque burden, yet worsens behavior and induces microglial inflammation in the APP/PS1 model of Alzheimer’s disease
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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. 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