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| Status |
Public on Oct 22, 2020 |
| Title |
Dysregulation of brain and choroid plexus cell types in severe COVID-19 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Though SARS-CoV-2 primarily targets the respiratory system, patients and survivors can suffer neurological symptoms. Yet, an unbiased understanding of the cellular and molecular processes affected in the brains of COVID-19 patients is still missing. Here, we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control (including 1 terminal influenza) and 8 COVID-19 patients. While a systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, we observe broad cellular perturbations which predict that choroid plexus barrier cells sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma. We discover COVID-19 disease-associated microglia and astrocyte subpopulations that share features with pathological cell states reported in human neurodegenerative disease. Synaptic signaling of upper-layer excitatory neurons—evolutionarily expanded in humans and linked to cognitive function—are preferentially affected in COVID-19. Across cell types, COVID-19 perturbations overlap with those in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia, and depression. Our findings and public dataset provide a molecular framework to understand COVID-19 related neurological disease observed now and which may emerge later.
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| Overall design |
Single-nuclei RNA transcriptomes of prefrontal cortex and choroid plexi tissue obtained from post-mortem brains of COVID-19, Influenza, and non-viral control patients using the 10x Genomics Drop-seq gene expression kit (v3.1).
Samples were sequenced at 150 bps paired-end configuration on a NovaSeq system. Index 1 contains sample indices (8 nts). Read 1 contains 10x cell barcode + UMI (28 nts). Read 2 contains the fragment insert (91 nts).
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| Contributor(s) |
Yang AC, Kern F, Losada PM, Maat CA, Schmartz GP, Fehlmann T, Schaum N, Lee DP, Calcuttawala K, Vest RT, Gate D, Berdnik D, McNerney WM, Cobos I, Ludwig N, Schulz-Schaeffer WJ, Keller A, Wyss-Coray T, Agam MR, Stein JA, Lu N, Hahn O, Channappa D |
| Citation(s) |
34153974 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| RF1 AG059694 |
Targeting Cerebrovascular TGF Signaling in Alzheimer's Disease |
PALO ALTO VETERANS INSTITUTE FOR RESEARCH |
TONY WYSS-CORAY |
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| Submission date |
Oct 21, 2020 |
| Last update date |
Sep 03, 2021 |
| Contact name |
Fabian Michael Kern |
| Organization name |
Saarland University
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| Department |
Center for Bioinformatics
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| Lab |
Chair for Clinical Bioinformatics
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| Street address |
Campus E2 1
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| City |
Saarbrücken |
| State/province |
Saarland |
| ZIP/Postal code |
66123 |
| Country |
Germany |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (30)
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| Relations |
| BioProject |
PRJNA670674 |
| SRA |
SRP288163 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE159812_RAW.tar |
944.0 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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