当前位置： SCI文献检索 > Clinical Epigenetics期刊下所有文献 > TWIST1 DNA methylation is a cell marker of airway and parenchymal lung fibroblasts that are differentially methylated in asthma.

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

Abstract：

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.

journal_name

Clin Epigenetics

journal_title

Clinical epigenetics

authors

Clifford RL,Yang CX,Fishbane N,Patel J,MacIsaac JL,McEwen LM,May ST,Castellanos-Uribe M,Nair P,Obeidat M,Kobor MS,Knox AJ,Hackett TL

doi

10.1186/s13148-020-00931-4

subject

Has Abstract

pub_date

2020-10-02 00:00:00

pages

145

issue

eissn

1868-7075

issn

1868-7083

pii

10.1186/s13148-020-00931-4

journal_volume

pub_type

杂志文章

在线工具

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