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Distinct microglia alternative splicing in Alzheimer's disease

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. GSE17...

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Autores principales: Lu, Yanjun, Tan, Lu, Xie, Jiazhao, Cheng, Liming, Wang, Xiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9467408/
https://www.ncbi.nlm.nih.gov/pubmed/36006403
http://dx.doi.org/10.18632/aging.204223
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author Lu, Yanjun
Tan, Lu
Xie, Jiazhao
Cheng, Liming
Wang, Xiong
author_facet Lu, Yanjun
Tan, Lu
Xie, Jiazhao
Cheng, Liming
Wang, Xiong
author_sort Lu, Yanjun
collection PubMed
description 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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spelling pubmed-94674082022-09-14 Distinct microglia alternative splicing in Alzheimer's disease Lu, Yanjun Tan, Lu Xie, Jiazhao Cheng, Liming Wang, Xiong Aging (Albany NY) Research Paper 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. Impact Journals 2022-08-23 /pmc/articles/PMC9467408/ /pubmed/36006403 http://dx.doi.org/10.18632/aging.204223 Text en Copyright: © 2022 Lu et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lu, Yanjun
Tan, Lu
Xie, Jiazhao
Cheng, Liming
Wang, Xiong
Distinct microglia alternative splicing in Alzheimer's disease
title Distinct microglia alternative splicing in Alzheimer's disease
title_full Distinct microglia alternative splicing in Alzheimer's disease
title_fullStr Distinct microglia alternative splicing in Alzheimer's disease
title_full_unstemmed Distinct microglia alternative splicing in Alzheimer's disease
title_short Distinct microglia alternative splicing in Alzheimer's disease
title_sort distinct microglia alternative splicing in alzheimer's disease
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9467408/
https://www.ncbi.nlm.nih.gov/pubmed/36006403
http://dx.doi.org/10.18632/aging.204223
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