Astrocytes and oligodendrocytes undergo subtype-specific transcriptional changes in Alzheimer's disease.
Alzheimer's disease
astrocyte
dataset integration
glia
heterogeneity
inflammation
neurodegeneration
oligodendrocyte
single-nuclei sequencing
spatial transcriptomics
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
01 06 2022
01 06 2022
Historique:
received:
22
03
2021
revised:
24
01
2022
accepted:
08
03
2022
pubmed:
6
4
2022
medline:
7
6
2022
entrez:
5
4
2022
Statut:
ppublish
Résumé
Resolving glial contributions to Alzheimer's disease (AD) is necessary because changes in neuronal function, such as reduced synaptic density, altered electrophysiological properties, and degeneration, are not entirely cell autonomous. To improve understanding of transcriptomic heterogeneity in glia during AD, we used single-nuclei RNA sequencing (snRNA-seq) to characterize astrocytes and oligodendrocytes from apolipoprotein (APOE) Ɛ2/3 human AD and age- and genotype-matched non-symptomatic (NS) brains. We enriched astrocytes before sequencing and characterized pathology from the same location as the sequenced material. We characterized baseline heterogeneity in both astrocytes and oligodendrocytes and identified global and subtype-specific transcriptomic changes between AD and NS astrocytes and oligodendrocytes. We also took advantage of recent human and mouse spatial transcriptomics resources to localize heterogeneous astrocyte subtypes to specific regions in the healthy and inflamed brain. Finally, we integrated our data with published AD snRNA-seq datasets, highlighting the power of combining datasets to resolve previously unidentifiable astrocyte subpopulations.
Identifiants
pubmed: 35381189
pii: S0896-6273(22)00244-6
doi: 10.1016/j.neuron.2022.03.008
pmc: PMC9167747
mid: NIHMS1795138
pii:
doi:
Substances chimiques
RNA, Small Nuclear
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1788-1805.e10Subventions
Organisme : NIA NIH HHS
ID : P30 AG008051
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066512
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG052909
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declarations of interests S.A.L. is a founder of AstronauTx Ltd and a member of its scientific advisory board. All other authors declare no competing interests.
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