Long-read transcript sequencing identifies differential isoform expression in the entorhinal cortex in a transgenic model of tau pathology.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 Aug 2024
02 Aug 2024
Historique:
received:
04
10
2023
accepted:
10
07
2024
medline:
3
8
2024
pubmed:
3
8
2024
entrez:
2
8
2024
Statut:
epublish
Résumé
Increasing evidence suggests that alternative splicing plays an important role in Alzheimer's disease (AD) pathology. We used long-read sequencing in combination with a novel bioinformatics tool (FICLE) to profile transcript diversity in the entorhinal cortex of female transgenic (TG) mice harboring a mutant form of human tau. Our analyses revealed hundreds of novel isoforms and identified differentially expressed transcripts - including specific isoforms of Apoe, App, Cd33, Clu, Fyn and Trem2 - associated with the development of tau pathology in TG mice. Subsequent profiling of the human cortex from AD individuals and controls revealed similar patterns of transcript diversity, including the upregulation of the dominant TREM2 isoform in AD paralleling the increased expression of the homologous transcript in TG mice. Our results highlight the importance of differential transcript usage, even in the absence of gene-level expression alterations, as a mechanism underpinning gene regulation in the development of AD neuropathology.
Identifiants
pubmed: 39095344
doi: 10.1038/s41467-024-50486-8
pii: 10.1038/s41467-024-50486-8
doi:
Substances chimiques
tau Proteins
0
Protein Isoforms
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6458Subventions
Organisme : Alzheimer's Research UK (ARUK)
ID : 573312
Organisme : Alzheimer's Research UK (ARUK)
ID : MR/W004984/1
Organisme : Alzheimer's Society
ID : 231
Pays : United Kingdom
Organisme : Wellcome Trust (Wellcome)
ID : WT097835MF
Organisme : Wellcome Trust (Wellcome)
ID : WT101650MA
Informations de copyright
© 2024. The Author(s).
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