Dynamic Dysregulation of Retrotransposons in Neurodegenerative Diseases at the Single-Cell Level\

Authors

Wankun Deng
Citu Citu
Andi Liu
Zhongming Zhao

Publication Date

10-29-2024

Journal

Genome Research

Abstract

Retrotransposable elements (RTEs) are common mobile genetic elements comprising ∼42% of the human genome. RTEs play critical roles in gene regulation and function, but how they are specifically involved in complex diseases is largely unknown. Here, we investigate the cellular heterogeneity of RTEs using 12 single-cell transcriptome profiles covering three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis. We identify cell type marker RTEs in neurons, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells that are related to these diseases. The differential expression analysis reveals the landscape of dysregulated RTE expression, especially L1s, in excitatory neurons of multiple neurodegenerative diseases. Machine learning algorithms for predicting cell disease stage using a combination of RTE and gene expression features suggests dynamic regulation of RTEs in AD. Furthermore, we construct a single-cell atlas of retrotransposable elements in neurodegenerative disease (scARE) using these data sets and features. scARE has six feature analysis modules to explore RTE dynamics in a user-defined condition. To our knowledge, scARE represents the first systematic investigation of RTE dynamics at the single-cell level within the context of neurodegenerative diseases.

Keywords

Humans, Retroelements, Single-Cell Analysis, Neurodegenerative Diseases, Alzheimer Disease, Neurons, Transcriptome, Parkinson Disease, Oligodendroglia, Gene Expression Regulation, Multiple Sclerosis, Astrocytes

DOI

10.1101/gr.279363.124

PMID

39424325

PMCID

PMC11529867

PubMedCentral® Posted Date

10-1-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes