Evidence map›Paper›PMID 35231079›Full record

ArticlePLoS pathogens2022

Identification of cell type specific ACE2 modifiers by CRISPR screening.

Emily J Sherman, Carmen Mirabelli, Vi T Tang, Taslima G Khan, Kyle Leix, Andrew A Kennedy, Sarah E Graham, Cristen J Willer, Andrew W Tai, Jonathan Z Sexton and 2 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Emily J ShermanDepartment of Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-3632-271X
Carmen MirabelliDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
Vi T TangDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-6079-9756
Taslima G KhanLife Sciences Institute, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-4778-6659
Kyle LeixDepartment of Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
Andrew A KennedyDepartment of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-3747-0597
Sarah E GrahamDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
Cristen J WillerDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
Andrew W TaiDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-6877-450X
Jonathan Z SextonDepartment of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-9244-5888
Christiane E WobusDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-5286-0924
Brian T EmmerDepartment of Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-7365-1021
University of Michigan · USMichigan United · US

Funding

University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
How flaviviruses hijack a host transmembrane protein chaperone to promote viral infectionR01GM139823 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TAI, ANDREW W. · 2021 to 2024
$1.4M
Cholesterol regulation by the cargo receptor SURF4K08HL148552 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI EMMER, BRIAN T · 2019 to 2023
$788k
NHLBI NIH HHS K08 HL148552NIDDK NIH HHS P30 DK034933NIGMS NIH HHS R01 GM139823
6 · The paper itself

Abstract

SARS-CoV-2 infection is initiated by binding of the viral spike protein to its receptor, ACE2, on the surface of host cells. ACE2 expression is heterogeneous both in vivo and in immortalized cell lines, but the molecular pathways that govern ACE2 expression remain unclear. We now report high-throughput CRISPR screens for functional modifiers of ACE2 surface abundance. In liver-derived HuH7 cells, we identified 35 genes whose disruption was associated with a change in the surface abundance of ACE2. Enriched among these ACE2 regulators were established transcription factors, epigenetic regulators, and functional networks. We further characterized individual HuH7 cell lines with disruption of SMAD4, EP300, PIAS1, or BAMBI and found these genes to regulate ACE2 at the mRNA level and to influence cellular susceptibility to SARS-CoV-2 infection. Orthogonal screening of lung-derived Calu-3 cells revealed a distinct set of ACE2 modifiers comprised of ACE2, KDM6A, MOGS, GPAA1, and UGP2. Collectively, our findings clarify the host factors involved in SARS-CoV-2 entry, highlight the cell type specificity of ACE2 regulatory networks, and suggest potential targets for therapeutic development.

Indexed as

COVID-19Angiotensin-Converting Enzyme 2Cell LineClustered Regularly Interspaced Short Palindromic RepeatsHumansSARS-CoV-2Spike Glycoprotein, CoronavirusAngiotensin-Converting Enzyme 2Spike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID35231079
PMCPMC8929698
OpenAlexW4214509802

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.