A single-cell atlas of entorhinal cortex from individuals with Alzheimer's disease reveals cell-type-specific gene expression regulation.
Alzheimer Disease
/ metabolism
Apolipoproteins E
/ metabolism
Astrocytes
/ metabolism
Atlases as Topic
Case-Control Studies
Down-Regulation
Entorhinal Cortex
/ metabolism
Female
Gene Expression Regulation
Genetic Predisposition to Disease
/ genetics
Humans
Male
Microglia
/ metabolism
Oligodendrocyte Precursor Cells
/ metabolism
Sequence Analysis, RNA
Up-Regulation
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
pubmed:
27
11
2019
medline:
1
2
2020
entrez:
27
11
2019
Statut:
ppublish
Résumé
There is currently little information available about how individual cell types contribute to Alzheimer's disease. Here we applied single-nucleus RNA sequencing to entorhinal cortex samples from control and Alzheimer's disease brains (n = 6 per group), yielding a total of 13,214 high-quality nuclei. We detail cell-type-specific gene expression patterns, unveiling how transcriptional changes in specific cell subpopulations are associated with Alzheimer's disease. We report that the Alzheimer's disease risk gene APOE is specifically repressed in Alzheimer's disease oligodendrocyte progenitor cells and astrocyte subpopulations and upregulated in an Alzheimer's disease-specific microglial subopulation. Integrating transcription factor regulatory modules with Alzheimer's disease risk loci revealed drivers of cell-type-specific state transitions towards Alzheimer's disease. For example, transcription factor EB, a master regulator of lysosomal function, regulates multiple disease genes in a specific Alzheimer's disease astrocyte subpopulation. These results provide insights into the coordinated control of Alzheimer's disease risk genes and their cell-type-specific contribution to disease susceptibility. These results are available at http://adsn.ddnetbio.com.
Identifiants
pubmed: 31768052
doi: 10.1038/s41593-019-0539-4
pii: 10.1038/s41593-019-0539-4
doi:
Substances chimiques
Apolipoproteins E
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2087-2097Subventions
Organisme : Medical Research Council
ID : MC_U120097112
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
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