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.
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TWIST 1 DNA甲基化是哮喘患者气道和肺实质成纤维细胞甲基化差异的细胞标志物。
DOI：
10.1186/s13148-020-00931-4
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发表时间：
2020-10-02
影响因子：
5.7
通讯作者：
Hackett TL
中科院分区：
文献类型：
--
作者：
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
间充质成纤维细胞是维持器官细胞外基质的普遍存在的细胞。在肺内，气道和实质成纤维细胞对肺发育至关重要，并随着疾病而改变，但由于缺乏独特的分子标记物，很难理解它们的作用。我们研究了来自健康和哮喘供体的气道和实质肺成纤维细胞的全基因组DNA甲基化和基因表达，以确定一种稳健的细胞标记物，并确定这些细胞在哮喘中是否具有分子差异。来自健康个体的气道（N = 8）和实质（N = 15）肺成纤维细胞在158个基因的表达和3936个CpG的DNA甲基化方面不同（Bonferroni调整的p值< 0.05）。细胞类型之间的差异DNA甲基化与42个基因的差异表达相关，但没有单一的DNA甲基化CpG特征（位置，效应大小，数量）定义的相互作用。在第二个队列中，基因表达和DNA甲基化的复制将TWIST 1基因表达、DNA甲基化和蛋白质表达鉴定为气道和实质肺成纤维细胞的细胞标志物，DNA甲基化具有100%的预测判别能力。在哮喘状态下，肺实质（112个区域）和气道成纤维细胞（17个区域）的DNA甲基化发生了差异性改变，区域之间没有重叠。TWIST 1的差异甲基化是气道和实质肺成纤维细胞的稳健细胞标志物。哮喘患者气道和肺实质成纤维细胞DNA甲基化的改变存在差异，这两种细胞类型在哮喘发病机制中的作用应予以考虑。
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. 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. 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.
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从头开始鉴定人基因组中差异甲基化区域。
影响因子：
3.9
作者：
Peters TJ;Buckley MJ;Statham AL;Pidsley R;Samaras K;V Lord R;Clark SJ;Molloy PL
通讯作者：
Molloy PL
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
8
作者：
Nicodemus-Johnson, Jessie;Myers, Rachel A.;Ober, Carole
通讯作者：
Ober, Carole
影响因子：
4.4
作者：
Schilling, Elinar;Rehli, Michael
通讯作者：
Rehli, Michael
影响因子：
3.7
作者：
Sandoval, Juan;Heyn, Holger A.;Esteller, Manel
通讯作者：
Esteller, Manel