Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer’s Disease
Nat Genet. 2021-07-08;53(8):1143-1155.
- Abstract
- The gene-regulatory landscape of the brain is highly dynamic in health and disease, coordinating a menagerie of biological processes across distinct cell-types. Here, we present a multi-omic single-nucleus study of 191,890 nuclei in late-stage Alzheimer’s Disease (AD), accessible through our web portal, profiling chromatin accessibility and gene expression in the same biological samples and uncovering vast cellular heterogeneity. We identified cell-type specific, disease-associated candidate cis-regulatory elements and their candidate target genes, including an oligodendrocyte-associated regulatory module containing links to APOE and CLU. We describe cis-regulatory relationships in specific cell-types at a subset of AD risk loci defined by genome wide association studies (GWAS), demonstrating the utility of this multi-omic single-nucleus approach. Trajectory analysis of glial populations identified disease-relevant transcription factors, like SREBF1, and their regulatory targets. Finally, we introduce scWGCNA, a co-expression network analysis strategy robust to sparse single-cell data, and perform a systems-level analysis of the AD transcriptome.
Related data
- Available data
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- Data summary
- All the multi-omics raw and processed data are available here
- Available data
- website
- File format
- other format
- Data summary
- The data can be accessed through online web app
- Available data
- website
- File format
- other format
- Data summary
- Raw sequencing data have been deposited into the National Center for Biotechnology Information Gene Expression Omnibus with accession numbers GSE174367.