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Series GSE193834 Query DataSets for GSE193834
Status Public on Jan 20, 2022
Title Bidirectional genome-wide CRISPR screens reveal host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs
Organism Homo sapiens
Experiment type Other
Summary Several genome-wide CRISPR knockout screens have been conducted to identify host factors regulating SARS-CoV-2 replication, but the models used have often relied on overexpression of ACE2 receptor and didn’t express TMPRSS2 protease, known to be important for viral entry at the plasma membrane. Here, we conducted a meta-analysis of these screens and showed a high level of cell-type specificity of the identified hits, arguing for the necessity to pursue efforts to uncover the full landscape of SARS-CoV-2 regulators. We performed genome-wide, bidirectional CRISPR screens in Calu-3 lung epithelial cells, as well as knockout screens in Caco-2 intestinal cells. As well as identifying ACE2 and TMPRSS2 as top hits, our study reveals a series of so far unidentified and critical host-dependency factors, including the Adaptins AP1G1 and AP1B1 and the flippase ATP8B1. Additionally, new anti-SARS-CoV-2 proteins with potent activity, including several membrane-associated Mucins (MUC1, MUC4 and MUC21), IL6R and CD44 were identified . We further observed that these genes mostly acted at the critical step of viral entry, with the notable exception of ATP8B1, the knockout of which prevented late stages of viral replication. Exploring the pro- and anti-viral breadth of these genes using highly pathogenic MERS-CoV, seasonal HCoV-NL63 and -229E and influenza A virus, we reveal that some genes such as AP1G1 and ATP8B1 are general coronavirus cofactors. In contrast, Mucins recapitulated their known role as a general antiviral defense mechanism. These results demonstrate the value of considering multiple cell models and perturbational modalities for understanding SARS-CoV-2 replication and provide a list of potential new targets for therapeutic interventions.
 
Overall design 37 samples analyzed, Control named:initial population, Selected population named: resistant population, replicates are included and mentioned below
 
Contributor(s) Rebendenne A, Roy P, Valadao A, Lee Y, DeWeirdt P, Hegde M, Doench J, Goujon C
Citation(s) 35879413
Submission date Jan 17, 2022
Last update date Aug 08, 2022
Contact name John G Doench
Organization name Broad Institute
Department Genetic Perturbation Platform
Street address 75 Ames St.
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (37)
GSM5822392 Calu-3 Cas9KO uninfected population screen 1.construct
GSM5822393 Calu-3 Cas9KO uninfected population screen 2.construct
GSM5822394 Calu-3 Cas9KO infected population screen 1.construct
Relations
BioProject PRJNA798057

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE193834_Supplementary_Data_10_Caco-2-ACE2_KO_SecondaryLibrary_Goujon.xlsx 345.6 Kb (ftp)(http) XLSX
GSE193834_Supplementary_Data_11_Calu-3_Cas9_KO_SecondaryLibrary_Goujon.xlsx 349.8 Kb (ftp)(http) XLSX
GSE193834_Supplementary_Data_12_Calu-3_Cas12a_KO_SecondaryLibrary_Goujon.xlsx 113.3 Kb (ftp)(http) XLSX
GSE193834_Supplementary_Data_13_A549-ACE2_Act_SecondaryLibrary_Goujon.xlsx 293.2 Kb (ftp)(http) XLSX
GSE193834_Supplementary_Data_14_Huh7.5.1-ACE2_Act_SecondaryLibrary_Goujon.xlsx 293.1 Kb (ftp)(http) XLSX
GSE193834_Supplementary_Data_15_Caco-2-ACE2_Act_SecondaryLibrary_Goujon.xlsx 292.0 Kb (ftp)(http) XLSX
GSE193834_Supplementary_Data_16_Calu-3_Act_SecondaryLibrary_Goujon.xlsx 318.1 Kb (ftp)(http) XLSX
GSE193834_Supplementary_Data_6_All_Secondary_KO_Screens_Goujon.xlsx 402.2 Kb (ftp)(http) XLSX
GSE193834_Supplementary_Data_7_All_Secondary_Act_Screens_Goujon.xlsx 251.6 Kb (ftp)(http) XLSX
GSE193834_Supplementary_Data_8_A549-ACE2_KO_SecondaryLibrary_Goujon.xlsx 346.0 Kb (ftp)(http) XLSX
GSE193834_Supplementary_Data_9_Huh7.5.1-ACE2_KO_SecondaryLibrary_Goujon.xlsx 408.3 Kb (ftp)(http) XLSX
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