ALS is imprinted in the chromatin accessibility of blood cells.
Chromatin remodeling
Epigenome
Integrated analysis
Motor neuron disease
Regulatory elements
Single-nuclei sequencing
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
24 Apr 2023
24 Apr 2023
Historique:
received:
12
12
2022
accepted:
27
03
2023
revised:
20
03
2023
medline:
26
4
2023
pubmed:
25
4
2023
entrez:
24
04
2023
Statut:
epublish
Résumé
Amyotrophic Lateral Sclerosis (ALS) is a complex and incurable neurodegenerative disorder in which genetic and epigenetic factors contribute to the pathogenesis of all forms of ALS. The interplay of genetic predisposition and environmental footprints generates epigenetic signatures in the cells of affected tissues, which then alter transcriptional programs. Epigenetic modifications that arise from genetic predisposition and systemic environmental footprints should in theory be detectable not only in affected CNS tissue but also in the periphery. Here, we identify an ALS-associated epigenetic signature ('epiChromALS') by chromatin accessibility analysis of blood cells of ALS patients. In contrast to the blood transcriptome signature, epiChromALS includes also genes that are not expressed in blood cells; it is enriched in CNS neuronal pathways and it is present in the ALS motor cortex. By combining simultaneous ATAC-seq and RNA-seq with single-cell sequencing in PBMCs and motor cortex from ALS patients, we demonstrate that epigenetic changes associated with the neurodegenerative disease can be found in the periphery, thus strongly suggesting a mechanistic link between the epigenetic regulation and disease pathogenesis.
Identifiants
pubmed: 37095391
doi: 10.1007/s00018-023-04769-w
pii: 10.1007/s00018-023-04769-w
pmc: PMC10126052
doi:
Substances chimiques
Chromatin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
131Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : DA 1657/2-1
Informations de copyright
© 2023. The Author(s).
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