Central lung gene expression associates with myofibroblast features in idiopathic pulmonary fibrosis.
Central lung gene expression associates with myofibroblast features in idiopathic pulmonary fibrosis.
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DOI：
10.1136/bmjresp-2022-001391
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发表时间：
2023-02
影响因子：
4.1
通讯作者：
Noth, Imre
中科院分区：
文献类型：
--
作者：
Huang, Yong;Guzy, Rob;Ma, Shwu-Fan;Bonham, Catherine A.;Jou, Jonathan;Schulte, Jefree J.;Kim, John S.;Barros, Andrew J.;Espindola, Milena S.;Husain, Aliya N.;Hogaboam, Cory M.;Sperling, Anne, I;Noth, Imre
中央肺组织在特发性肺纤维化（IPF）发病机制中的作用尚不清楚。使用RNA测序（RNA-seq）转录组确定IPF-中央和IPF-外周肺外植体细胞类型之间的关系。通过回顾H&E数据，选择成对的IPF-中心和IPF-外周沿着与非IPF肺的活检。差异表达基因（DEG）的标准设定为错误发现率<5% and fold change >2。进行计算细胞组成去卷积。计算每种细胞类型的特征评分。比较中心性IPF与非IPF，确定了1723例DEG（1522例上调，201例下调）。与非IPF相比，中央IPF基因中62%（938/1522）的相互上调基因在外周IPF中也上调。此外，85个IPF中枢相关基因（CAG）在中枢性IPF中相对于外周性IPF和中枢性非IPF均上调。IPF单细胞RNA-seq分析显示肌成纤维细胞中CAG特征评分最高，与先前发表的活化成纤维细胞特征显著相关（r=0.88，p=1.6×10−4）。IPF患者的CAG特征评分显著高于非IPF肌成纤维细胞（p=0.013）。中央型IPF基因的网络分析确定了一个与中央型IPF中肌成纤维细胞的去卷积比例显著相关的模块，并且与外周型IPF中的炎症灶特征反相关。模块基因在特发性肺纤维化信号通路中过度表达。中央IPF肺区域的基因表达显示了有助于疾病进展的活跃肌成纤维细胞特征。进一步阐明相对免于形态学重排的IPF肺中心区域细胞的病理转录组学状态，可能有助于了解IPF进展中的分子变化。
Contribution of central lung tissues to pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unknown. To ascertain the relationship between cell types of IPF-central and IPF-peripheral lung explants using RNA sequencing (RNA-seq) transcriptome. Biopsies of paired IPF-central and IPF-peripheral along with non-IPF lungs were selected by reviewing H&E data. Criteria for differentially expressed genes (DEG) were set at false discovery rate <5% and fold change >2. Computational cell composition deconvolution was performed. Signature scores were computed for each cell type. Comparison of central IPF versus non-IPF identified 1723 DEG (1522 upregulated and 201 downregulated). Sixty-two per cent (938/1522) of the mutually upregulated genes in central IPF genes were also upregulated in peripheral IPF versus non-IPF. Moreover, 85 IPF central-associated genes (CAG) were upregulated in central IPF versus both peripheral IPF and central non-IPF. IPF single-cell RNA-seq analysis revealed the highest CAG signature score in myofibroblasts and significantly correlated with a previously published activated fibroblasts signature (r=0.88, p=1.6×10−4). CAG signature scores were significantly higher in IPF than in non-IPF myofibroblasts (p=0.013). Network analysis of central-IPF genes identified a module significantly correlated with the deconvoluted proportion of myofibroblasts in central IPF and anti-correlated with inflammation foci trait in peripheral IPF. The module genes were over-represented in idiopathic pulmonary fibrosis signalling pathways. Gene expression in central IPF lung regions demonstrates active myofibroblast features that contributes to disease progression. Further elucidation of pathological transcriptomic state of cells in the central regions of the IPF lung that are relatively spared from morphological rearrangements may provide insights into molecular changes in the IPF progression.
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影响因子：
24.5
作者：
Roderfeld, Martin;Rath, Timo;Roeb, Elke
通讯作者：
Roeb, Elke
DOI：
10.1164/rccm.201403-0509pp
发表时间：
2014-10-15
影响因子：
24.7
作者：
Ahluwalia, Neil;Shea, Barry S.;Tager, Andrew M.
通讯作者：
Tager, Andrew M.
DOI：
10.1164/rccm.200504-644oc
发表时间：
2006-01-15
影响因子：
24.7
作者：
Selman, M;Pardo, A;Zlotnik, A
通讯作者：
Zlotnik, A
影响因子：
5
作者：
Jonsdottir, Hulda R.;Arason, Ari J.;Magnusson, Magnus K.
通讯作者：
Magnusson, Magnus K.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y