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Updated: Oct 1, 2025
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Cell Surface Receptor Identification Using Genome-Scale CRISPR/Cas9 Genetic Screens
Published on: June 6, 2020
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Identification of cell type specific ACE2 modifiers by CRISPR screening
Emily J Sherman1, Carmen Mirabelli2, Vi T Tang3,4
1Department of Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
Plos Pathogens
|March 1, 2022
Summary
Researchers identified key host genes controlling the surface abundance of Angiotensin-Converting Enzyme 2 (ACE2), a crucial receptor for SARS-CoV-2 entry. This discovery offers potential new therapeutic targets for COVID-19 treatment.
Area of Science:
- Virology
- Genetics
- Cell Biology
Background:
- SARS-CoV-2 uses the ACE2 receptor on host cells for viral entry.
- ACE2 expression varies significantly, and the underlying molecular mechanisms are not fully understood.
Purpose of the Study:
- To identify host factors that regulate the surface abundance of ACE2.
- To understand the cell-type specificity of ACE2 regulatory networks.
- To uncover potential therapeutic targets for SARS-CoV-2 infection.
Main Methods:
- High-throughput CRISPR screens were employed to identify genes influencing ACE2 surface levels.
- Functional validation was performed on specific gene disruptions in liver (HuH7) and lung (Calu-3) cell lines.
- ACE2 mRNA levels and cellular susceptibility to SARS-CoV-2 infection were assessed.
Main Results:
- In HuH7 cells, disruption of 35 genes altered ACE2 surface abundance, including transcription factors and epigenetic regulators.
- SMAD4, EP300, PIAS1, and BAMBI were confirmed to regulate ACE2 mRNA and SARS-CoV-2 susceptibility.
- Calu-3 cells exhibited a distinct set of ACE2 modifiers, including ACE2 itself, KDM6A, MOGS, GPAA1, and UGP2.
Conclusions:
- Host factors significantly influence ACE2 surface expression and SARS-CoV-2 entry.
- ACE2 regulatory networks show cell-type specificity.
- Identified host factors represent potential therapeutic targets for mitigating SARS-CoV-2 infection.
