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

Clifford, Rachel L.; Yang, Chen Xi; Fishbane, Nick; Patel, Jamie; MacIsaac, Julia L.; McEwen, Lisa M.; May, Sean T.; Castellanos-Uribe, Marcos; Nair, Parameswaran; Obeidat, Ma�en; Kobor, Michael S.; Knox, Alan J.; Hackett, Tillie Louise

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


Authors

Chen Xi Yang

Nick Fishbane

Jamie Patel

Julia L. MacIsaac

Lisa M. McEwen

Marcos Castellanos-Uribe

Parameswaran Nair

Ma�en Obeidat

Michael S. Kobor

Alan J. Knox

Tillie Louise Hackett



Abstract

© 2020 The Author(s). Background: Mesenchymal 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. Results: Airway (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. Conclusions: Differential 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.

Citation

Clifford, R. L., Yang, C. X., Fishbane, N., Patel, J., MacIsaac, J. L., McEwen, L. M., May, S. T., Castellanos-Uribe, M., Nair, P., Obeidat, M., Kobor, M. S., Knox, A. J., & Hackett, T. L. (2020). TWIST1 DNA methylation is a cell marker of airway and parenchymal lung fibroblasts that are differentially methylated in asthma. Clinical Epigenetics, 12(1), Article 145. https://doi.org/10.1186/s13148-020-00931-4

Journal Article Type Article
Acceptance Date Sep 1, 2020
Online Publication Date Oct 2, 2020
Publication Date 2020-12
Deposit Date Oct 16, 2020
Publicly Available Date Oct 16, 2020
Journal Clinical Epigenetics
Print ISSN 1868-7075
Electronic ISSN 1868-7083
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 12
Issue 1
Article Number 145
DOI https://doi.org/10.1186/s13148-020-00931-4
Keywords Genetics(clinical); Developmental Biology; Genetics; Molecular Biology
Public URL https://nottingham-repository.worktribe.com/output/4939107
Publisher URL https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00931-4

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