Evidence map›Paper›PMID 26043872›Full record

ArticleGene therapy2015

CRISPR-Cas9-mediated gene knockout in primary human airway epithelial cells reveals a proinflammatory role for MUC18.

H W Chu, C Rios, C Huang, A Wesolowska-Andersen, E G Burchard, B P O'Connor, T E Fingerlin, D Nichols, S D Reynolds, M A Seibold

Open access · greenAbstract read
In one paragraph

Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

66 citing papers in PubMed, 100 citations in OpenAlex.

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  13. A comparative study ofbioRxiv : the preprint server for biology · 2023
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  20. Temporal Whole-Transcriptomic Analysis of CharacterizedFrontiers in cell and developmental biology · 2022
    Article

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

H W ChuDepartment of Medicine, National Jewish Health, Denver, CO, USA.
C RiosIntegrated Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
C HuangDepartment of Medicine, National Jewish Health, Denver, CO, USA.
A Wesolowska-AndersenIntegrated Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
E G BurchardDepartment of Medicine, University of California-San Francisco, San Francisco, CA, USA.
B P O'ConnorIntegrated Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
T E FingerlinIntegrated Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
D NicholsDepartment of Pediatrics, National Jewish Health, Denver, CO, USA.
S D ReynoldsDepartment of Pediatrics, National Jewish Health, Denver, CO, USA.
M A SeiboldIntegrated Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
National Jewish Health · USUniversity of Colorado Denver · USUniversity of California, San Francisco · US

Funding

Role of miRNAs in Th2-Driven inflammation in AsthmaP01HL107202 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANSEL, KARL MARK · 2012 to 2023
$23.3M
IRAK-M in lung defense against rhinovirus infectionR01AI106287 · NIAID · NATIONAL JEWISH HEALTH · PI CHU, HONG W, LI, LIWU · 2014 to 2018
$2.0M
Novel function of MUC18: amplification of inflammation in allergic lungsR01HL122321 · NHLBI · NATIONAL JEWISH HEALTH · PI CHU, HONG W · 2015 to 2018
$1.6M
NHLBI NIH HHS P01 HL107202NHLBI NIH HHS R01 HL122321NIAID NIH HHS R01 AI106287
6 · The paper itself

Abstract

Targeted knockout of genes in primary human cells using CRISPR-Cas9-mediated genome-editing represents a powerful approach to study gene function and to discern molecular mechanisms underlying complex human diseases. We used lentiviral delivery of CRISPR-Cas9 machinery and conditional reprogramming culture methods to knockout the MUC18 gene in human primary nasal airway epithelial cells (AECs). Massively parallel sequencing technology was used to confirm that the genome of essentially all cells in the edited AEC populations contained coding region insertions and deletions (indels). Correspondingly, we found mRNA expression of MUC18 was greatly reduced and protein expression was absent. Characterization of MUC18 knockout cell populations stimulated with TLR2, 3 and 4 agonists revealed that IL-8 (a proinflammatory chemokine) responses of AECs were greatly reduced in the absence of functional MUC18 protein. Our results show the feasibility of CRISPR-Cas9-mediated gene knockouts in AEC culture (both submerged and polarized), and suggest a proinflammatory role for MUC18 in airway epithelial response to bacterial and viral stimuli.

Indexed as

Genetic VectorsLentivirusCD146 AntigenClustered Regularly Interspaced Short Palindromic RepeatsGene ExpressionGene Knockout TechniquesHumansInflammationPrimary Cell CultureRespiratory MucosaCD146 AntigenMCAM protein, human

Identifiers

PMID26043872
PMCPMC4600011
OpenAlexW1603039152

What OpenQuestion holds

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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.