Analysis of differential gene expression and transcript usage in hippocampus of Apoe null mutant mice: Implications for Alzheimer's disease. (March 2022)

• Record Type: Journal Article
• Authors: Weller, Andrew E.; Doyle, Glenn A.; Reiner, Benjamin C.; Crist, Richard C.; Berrettini, Wade H.
• Is Part Of: Neuroscience research. Volume 176(2022)
• Page Start: 85
• Page End: 89
• Publication Date: 2022-03
• Subjects: Alzheimer's disease (AD) -- Apolipoprotein E (APOE) -- Knockout mouse -- Single-nucleus RNA sequencing (snRNAseq) -- Differential gene expression -- Differential transcript usage; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2021.10.010
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: Single cell based analyses promote greater understanding of Alzheimer's disease. Mitochondrial function and energy production are implicated in a mouse model. Mouse Apoe is involved in the generation of specific polyadenylated transcripts. Single cell studies could inform treatments that target specific brain cell types. Abstract: A dataset of single-nucleus RNA sequencing (snRNAseq) data was analyzed using Seurat, Sierra, and Ingenuity Pathway Analysis (IPA) programs to assess differentially expressed genes (DEGs) and differential transcript usage (DTU) in mouse hippocampal cell types. Seurat identified DEGs between the wild type (WT) and Apoe knockout (EKO) mice. IPA identified 11 statistically significant canonical pathways in >1 cell type. Sierra identified Sipa1l1 with DTU between WT and EKO samples. Analysis of the Sipa1l1 peak region identified an alternative non-canonical polyadenylation signal and a putative cytoplasmic polyadenylation element. APOE regulation of gene transcription and co-transcriptional RNA processing may underlie Alzheimer's disease.