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| Status |
Public on Oct 24, 2020 |
| Title |
Identification of required host factors for SARS-CoV-2 infection in human cells [ECCITE-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
To better understand host-virus genetic dependencies and find potential therapeutic targets for COVID-19, we performed a genome-scale CRISPR loss-of-function screen to identify host factors required for SARS-CoV-2 viral infection of human alveolar epithelial cells. Top-ranked genes cluster into distinct pathways, including the vacuolar ATPase proton pump, Retromer, and Commander complexes. We validate these gene targets using several orthogonal methods such as CRISPR knock-out, RNA interference knock-down, and small-molecule inhibitors. Using single-cell RNA- sequencing, we identify shared transcriptional changes in cholesterol biosynthesis upon loss of top-ranked genes. In addition, given the key role of the ACE2 receptor in the early stages of viral entry, we show that loss of RAB7A reduces viral entry by sequestering the ACE2 receptor inside cells. Overall, this work provides a genome- scale, quantitative resource of the impact of the loss of each host gene on fitness/response to viral infection.
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| Overall design |
Identification of systemic changes upon SARS-CoV-2 entry hit gene perturbation using ECCITE-seq.
ECCITE-seq (Expanded CRISPR-compatible Cellular Indexing of Transcriptomes and Epitopes by sequencing)
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| Web link |
https://0-doi-org.brum.beds.ac.uk/10.1016/j.cell.2020.10.030
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| Contributor(s) |
Wessels H |
| Citation(s) |
33147445 |
| Submission date |
Oct 19, 2020 |
| Last update date |
Jan 23, 2021 |
| Contact name |
Zharko Daniloski |
| E-mail(s) |
zd315@nyu.edu
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| Organization name |
New York University
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| Department |
Biology
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| Street address |
1 Washington square village, 2P
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| City |
New York City |
| State/province |
New York |
| ZIP/Postal code |
10012 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA669984 |
| SRA |
SRP287801 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE159519_ECCITE_metadata.tsv.gz |
864.8 Kb |
(ftp)(http) |
TSV |
| GSE159519_GDO_Barcode_revcomp.csv.gz |
1.1 Kb |
(ftp)(http) |
CSV |
| GSE159519_HTO_Barcode.csv.gz |
231 b |
(ftp)(http) |
CSV |
| GSE159519_RAW.tar |
787.4 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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