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| Status |
Public on Oct 16, 2019 |
| Title |
A single-cell atlas of the human cortex reveals drivers of transcriptional changes in Alzheimer’s disease in specific cell subpopulations |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
There is currently little information about how individual cell types contribute to Alzheimer’s disease (AD). Here, we applied single-nucleus RNA-seq (snRNA-seq) on the entorhinal cortex from control and AD brains of twelve individuals, 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 contribute to AD. We report that the AD risk gene, APOE, is specifically repressed in AD oligodendrocyte progenitor cells and astrocyte subpopulations, and upregulated in an AD-specific microglial subopulation. Integrating transcription factor regulatory modules with AD risk loci revealed drivers of cell-type-specific fate transitions towards AD. For example, transcription factor EB, a master regulator of lysosomal function, regulates multiple disease genes in a specific AD astrocyte sub-population. These results provide insights into the coordinated control of AD risk genes and their cell-type specific contribution to disease susceptibility and are available at http://adsn.ddnetbio.com.
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| Overall design |
Single Nuclei RNA sequencing of 8 10x libraries with each library containing 2 individuals (n =16)
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| Contributor(s) |
Chew G, Grubman A, Ouyang JF, Rackham O, Polo J, Petretto E |
| Citation(s) |
31768052 |
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| Submission date |
Oct 15, 2019 |
| Last update date |
Dec 05, 2019 |
| Contact name |
Gabriel Chew |
| E-mail(s) |
e0008504@u.nus.edu
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| Organization name |
Duke-NUS Medical School
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| Street address |
8 College Road
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| City |
Singapore |
| ZIP/Postal code |
169857 |
| Country |
Singapore |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (8)
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| GSM4120422 |
Human Entorhinal Cortex of aged AD individuals AD7-AD8 |
| GSM4120423 |
Human Entorhinal Cortex of aged AD individuals AD5-AD6 |
| GSM4120424 |
Human Entorhinal Cortex of aged AD individuals AD3-AD4 |
| GSM4120425 |
Human Entorhinal Cortex of aged Healthy individuals Ct5-Ct6 |
| GSM4120426 |
Human Entorhinal Cortex of aged Healthy individuals Ct3-Ct4 |
| GSM4120427 |
Human Entorhinal Cortex of aged Healthy individuals Ct1-Ct2 |
| GSM4120428 |
Human Entorhinal Cortex of aged Healthy individuals Ct7-Ct8 |
| GSM4120429 |
Human Entorhinal Cortex of aged AD individuals AD1-AD2 |
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| Relations |
| BioProject |
PRJNA577618 |
| SRA |
SRP225693 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE138852_counts.csv.gz |
11.9 Mb |
(ftp)(http) |
CSV |
| GSE138852_covariates.csv.gz |
84.8 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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