Evidence map›Paper›PMID 34354120›Full record

ArticleScientific reports2021

ACE2 protein expression within isogenic cell lines is heterogeneous and associated with distinct transcriptomes.

Emily J Sherman, Brian T Emmer

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.1field-weighted citation impact, top 11% 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

28 citing papers in PubMed, 38 citations in OpenAlex.

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  7. Interactions of SARS-CoV-2 with Human Target Cells-A Metabolic View.International journal of molecular sciences · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Emily J ShermanDepartment of Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, MI, USA.
Brian T EmmerDepartment of Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, MI, USA. bemmer@med.umich.edu.
University of Michigan–Ann Arbor · US

Funding

Cholesterol regulation by the cargo receptor SURF4K08HL148552 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI EMMER, BRIAN T · 2019 to 2023
$788k
National Heart, Lung, and Blood Institute,United States K08-HL148552NHLBI NIH HHS K08 HL148552
6 · The paper itself

Abstract

The membrane protein angiotensin-converting enzyme 2 (ACE2) is a physiologic regulator of the renin-angiotensin system and the cellular receptor for the SARS-CoV-2 virus. Prior studies of ACE2 expression have primarily focused on mRNA abundance, with investigation at the protein level limited by uncertain specificity of commercial ACE2 antibodies. Here, we report our development of a sensitive and specific flow cytometry-based assay for cellular ACE2 protein abundance. Application of this approach to multiple cell lines revealed an unexpected degree of cellular heterogeneity, with detectable ACE2 protein in only a subset of cells in each isogenic population. This heterogeneity was mediated at the mRNA level by transcripts predominantly initiated from the ACE2 proximal promoter. ACE2 expression was heritable but not fixed over multiple generations of daughter cells, with gradual drift toward the original heterogeneous background. RNA-seq profiling identified distinct transcriptomes of ACE2-expressing relative cells to non-expressing cells, with enrichment in functionally related genes and transcription factor target sets. Our findings provide a validated approach for the specific detection of ACE2 protein at the surface of single cells, support an epigenetic mechanism of ACE2 gene regulation, and identify specific pathways associated with ACE2 expression in HuH7 cells.

Indexed as

TranscriptomeAngiotensin-Converting Enzyme 2Cell LineCOVID-19Gene ExpressionGene Expression ProfilingGene Expression RegulationHumansReceptors, VirusRNA, MessengerSARS-CoV-2ACE2 protein, humanAngiotensin-Converting Enzyme 2Receptors, VirusRNA, Messenger

Identifiers

PMID34354120
PMCPMC8342525
OpenAlexW3190762240

What OpenQuestion holds

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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.