Smoking dysregulates the human airway basal cell transcriptome at COPD risk locus 19q13.2.
Smoking dysregulates the human airway basal cell transcriptome at COPD risk locus 19q13.2.
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DOI：
10.1371/journal.pone.0088051
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Crystal RG
中科院分区：
文献类型：
--
作者：
Ryan DM;Vincent TL;Salit J;Walters MS;Agosto-Perez F;Shaykhiev R;Strulovici-Barel Y;Downey RJ;Buro-Auriemma LJ;Staudt MR;Hackett NR;Mezey JG;Crystal RG
全基因组关联研究和候选基因研究已经确定了一些与吸烟相关疾病COPD相关的危险基因，COPD是一种起源于呼吸道上皮的疾病。由于呼吸道基底细胞(BC)干/祖细胞最早表现出与吸烟相关的异常(增生、鳞状化生)，我们假设吸烟者BC存在转录异常，部分富含在已知的GWAs/候选基因位点。采用大规模平行测序法比较健康非吸烟者(n = 10)和健康吸烟者(n = 7)呼吸道上皮中BC的转录组。将差异表达基因的染色体位置与GWAS确定的基因位置进行比较，以增加患COPD的风险。与非吸烟者BC相比，吸烟者BC有676个基因差异表达，主要是吸烟上调。值得注意的是，这些基因中有166个(25%)位于19号染色体上，其中13个基因定位于19q13.2(与Chance相比，p<；10−4)，包括4个与慢性阻塞性肺疾病风险相关的基因(NFKBIB、LTBP4、EGLN2和TGFB1)。这些观察首次提供了吸烟相关肺部疾病的已知遗传风险与呼吸道BC之间的第一个直接联系，BC是与吸烟相关的最早发生变化的肺细胞数量。
Genome-wide association studies (GWAS) and candidate gene studies have identified a number of risk loci associated with the smoking-related disease COPD, a disorder that originates in the airway epithelium. Since airway basal cell (BC) stem/progenitor cells exhibit the earliest abnormalities associated with smoking (hyperplasia, squamous metaplasia), we hypothesized that smoker BC have a dysregulated transcriptome, enriched, in part, at known GWAS/candidate gene loci. Massive parallel RNA sequencing was used to compare the transcriptome of BC purified from the airway epithelium of healthy nonsmokers (n = 10) and healthy smokers (n = 7). The chromosomal location of the differentially expressed genes was compared to loci identified by GWAS to confer risk for COPD. Smoker BC have 676 genes differentially expressed compared to nonsmoker BC, dominated by smoking up-regulation. Strikingly, 166 (25%) of these genes are located on chromosome 19, with 13 localized to 19q13.2 (p<10−4 compared to chance), including 4 genes (NFKBIB, LTBP4, EGLN2 and TGFB1) associated with risk for COPD. These observations provide the first direct connection between known genetic risks for smoking-related lung disease and airway BC, the population of lung cells that undergo the earliest changes associated with smoking.
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影响因子：
64.8
作者：
Colaluca, Ivan N.;Tosoni, Daniela;Di Fiore, Pier Paolo
通讯作者：
Di Fiore, Pier Paolo
DOI：
10.4161/cc.21404
发表时间：
2012-09-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Becker W
通讯作者：
Becker W
影响因子：
3.7
作者：
Hackett NR;Shaykhiev R;Walters MS;Wang R;Zwick RK;Ferris B;Witover B;Salit J;Crystal RG
通讯作者：
Crystal RG
影响因子：
158.5
作者：
AUERBACH, O;GERE, JB;STOUT, AP
通讯作者：
STOUT, AP
DOI：
10.1164/ajrccm.158.6.9803053
发表时间：
1998-12-01
影响因子：
24.7
作者：
de Boer, WI;van Schadewijk, A;van Krieken, JHJM
通讯作者：
van Krieken, JHJM