Research Paper Volume 14, Issue 16 pp 6554—6566
Distinct microglia alternative splicing in Alzheimer's disease
- 1 Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 2 Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China
- 3 Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Received: May 11, 2022 Accepted: August 3, 2022 Published: August 23, 2022
https://doi.org/10.18632/aging.204223How to Cite
Copyright: © 2022 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
AS: alternative splicing; 5′SS: 5′ splice site; 3′SS: 3′ splice site; A3SS: alternative 3′SS; SE: skipped exon; RI: retained intron; A5SS: alternative 5′SS; MXE: mutually exclusive exons; AD: Alzheimer’s disease; PSI: percent spliced in; GO: gene ontology; PCA: principal component analysis; NMD: nonsense-mediated mRNA decay.