Evidence map›Paper›PMID 33008450›Full record

ArticleClinical epigenetics2020

TWIST1 DNA methylation is a cell marker of airway and parenchymal lung fibroblasts that are differentially methylated in asthma.

Rachel L Clifford, Chen Xi Yang, Nick Fishbane, Jamie Patel, Julia L MacIsaac, Lisa M McEwen, Sean T May, Marcos Castellanos-Uribe, Parameswaran Nair, Ma'en Obeidat and 3 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

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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

13 authors at 4 institutions in 2 countries.

Rachel L CliffordNottingham NIHR Biomedical Research Centre, Nottingham MRC Molecular Pathology Node, Division of Respiratory Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital, Nottingham, UK. r.clifford@nottingham.ac.uk.ORCID 0000-0002-8677-452X
Chen Xi YangCentre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada.
Nick FishbaneCentre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada.
Jamie PatelNottingham NIHR Biomedical Research Centre, Nottingham MRC Molecular Pathology Node, Division of Respiratory Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital, Nottingham, UK.
Julia L MacIsaacBC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Lisa M McEwenBC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Sean T MayNottingham Arabidopsis Stock Centre, Plant Sciences Building, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
Marcos Castellanos-UribeNottingham Arabidopsis Stock Centre, Plant Sciences Building, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
Parameswaran NairFirestone Institute for Respiratory Health, St Joseph's Healthcare and Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Ma'en ObeidatCentre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada.
Michael S KoborBC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Alan J KnoxNottingham NIHR Biomedical Research Centre, Nottingham MRC Molecular Pathology Node, Division of Respiratory Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital, Nottingham, UK.
Tillie-Louise HackettCentre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada.
University of British Columbia · CANottingham University Hospitals NHS Trust · GBUniversity of Nottingham · GBSt. Joseph’s Healthcare Hamilton · CA

Funding

Biotechnology and Biological Sciences Research Council BB/E022758/1Biotechnology and Biological Sciences Research Council BB/I001271/1CIHRMedical Research Council MR/N005953/1MRF_ MRF-009-0004-RG-CLIFFMRF_ MRF-091-0008-RG-CLIFF
6 · The paper itself

Abstract

backgroundMesenchymal fibroblasts are ubiquitous cells that maintain the extracellular matrix of organs. Within the lung, airway and parenchymal fibroblasts are crucial for lung development and are altered with disease, but it has been difficult to understand their roles due to the lack of distinct molecular markers. We studied genome-wide DNA methylation and gene expression in airway and parenchymal lung fibroblasts from healthy and asthmatic donors, to identify a robust cell marker and to determine if these cells are molecularly distinct in asthma.

resultsAirway (N = 8) and parenchymal (N = 15) lung fibroblasts from healthy individuals differed in the expression of 158 genes, and DNA methylation of 3936 CpGs (Bonferroni adjusted p value < 0.05). Differential DNA methylation between cell types was associated with differential expression of 42 genes, but no single DNA methylation CpG feature (location, effect size, number) defined the interaction. Replication of gene expression and DNA methylation in a second cohort identified TWIST1 gene expression, DNA methylation and protein expression as a cell marker of airway and parenchymal lung fibroblasts, with DNA methylation having 100% predictive discriminatory power. DNA methylation was differentially altered in parenchymal (112 regions) and airway fibroblasts (17 regions) with asthmatic status, with no overlap between regions.

conclusionsDifferential methylation of TWIST1 is a robust cell marker of airway and parenchymal lung fibroblasts. Airway and parenchymal fibroblast DNA methylation are differentially altered in individuals with asthma, and the role of both cell types should be considered in the pathogenesis of asthma.

Indexed as

AgedAirway RemodelingAsthmaBiomarkersCase-Control StudiesCpG IslandsDNA MethylationFemaleFibroblastsGene ExpressionGenome-Wide Association StudyHumansLungMaleMiddle AgedNuclear ProteinsBiomarkersNuclear ProteinsTWIST1 protein, humanTwist-Related Protein 1AirwayAsthmaCell markerDNA methylationFibroblastGene expressionLungParenchyma

Identifiers

PMID33008450
PMCPMC7531162
OpenAlexW3089820751

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.