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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2022
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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. |
format | Online Article Text |
id | pubmed-9467408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
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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