Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD.
Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD.
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单细胞RNA测序鉴定IGFBP5和QKI为与严重COPD相关的纤毛上皮细胞基因。
DOI：
10.1186/s12931-021-01675-2
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发表时间：
2021-04-06
影响因子：
5.8
通讯作者：
Nyunoya T
中科院分区：
文献类型：
--
作者：
Li X;Noell G;Tabib T;Gregory AD;Trejo Bittar HE;Vats R;Kaminski TW;Sembrat J;Snyder ME;Chandra D;Chen K;Zou C;Zhang Y;Sundd P;McDyer JF;Sciurba F;Rojas M;Lafyatis R;Shapiro SD;Faner R;Nyunoya T
慢性阻塞性肺疾病（COPD）的全肺组织转录组学分析研究已经鉴定出与气流受限严重程度和/或肺气肿存在相关的几个基因，然而，驱动这些基因表达特征的细胞类型仍然未被鉴定。为了确定重度COPD中细胞特异性转录组学的变化，我们对来自无基础肺病的非吸烟受试者（n = 3）和重度COPD患者（n = 3）的外周肺实质组织的n = 29，961个细胞进行了单细胞RNA测序（scRNA seq）。评估细胞类型组成和细胞特异性基因表达特征。使用基因集富集分析（GSEA）来鉴定促成先前报道的转录组签名的特定细胞类型。scRNA seq数据的T分布随机邻居嵌入和聚类揭示了总共17个不同的群体。其中，病例组与对照组相比具有更多差异表达基因的群体（对数倍数变化>| 0.4| FDR = 0.05）分别为：单核细胞（n = 1499）、巨噬细胞（n = 868）和纤毛上皮细胞（n = 590）。使用GSEA，我们发现只有纤毛和细胞毒性T细胞表现出富集先前报道的127个局部肺气肿基因特征的趋势（标准化富集分数[内斯]分别为= 1.28和= 1.33，FDR = 0.085和= 0.092）。在COPD肺的纤毛上皮细胞中存在的显著改变的基因中，还发现QKI和IGFBP 5蛋白水平在COPD肺中改变。scRNA seq可用于以细胞类型特异性方式鉴定可能有助于肺气肿发展的转录变化和可能的个体蛋白质水平。在线版本包含补充材料，可通过10.1186/s12931-021-01675-2获得。
Whole lung tissue transcriptomic profiling studies in chronic obstructive pulmonary disease (COPD) have led to the identification of several genes associated with the severity of airflow limitation and/or the presence of emphysema, however, the cell types driving these gene expression signatures remain unidentified. To determine cell specific transcriptomic changes in severe COPD, we conducted single-cell RNA sequencing (scRNA seq) on n = 29,961 cells from the peripheral lung parenchymal tissue of nonsmoking subjects without underlying lung disease (n = 3) and patients with severe COPD (n = 3). The cell type composition and cell specific gene expression signature was assessed. Gene set enrichment analysis (GSEA) was used to identify the specific cell types contributing to the previously reported transcriptomic signatures. T-distributed stochastic neighbor embedding and clustering of scRNA seq data revealed a total of 17 distinct populations. Among them, the populations with more differentially expressed genes in cases vs. controls (log fold change >|0.4| and FDR = 0.05) were: monocytes (n = 1499); macrophages (n = 868) and ciliated epithelial cells (n = 590), respectively. Using GSEA, we found that only ciliated and cytotoxic T cells manifested a trend towards enrichment of the previously reported 127 regional emphysema gene signatures (normalized enrichment score [NES] = 1.28 and = 1.33, FDR = 0.085 and = 0.092 respectively). Among the significantly altered genes present in ciliated epithelial cells of the COPD lungs, QKI and IGFBP5 protein levels were also found to be altered in the COPD lungs. scRNA seq is useful for identifying transcriptional changes and possibly individual protein levels that may contribute to the development of emphysema in a cell-type specific manner. The online version contains supplementary material available at 10.1186/s12931-021-01675-2.
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影响因子：
30.8
作者：
Ebersole, TA;Chen, Q;Artzt, K
通讯作者：
Artzt, K
影响因子：
10
作者：
Lamontagne, Maxime;Timens, Wim;Postma, Dirkje S.
通讯作者：
Postma, Dirkje S.
使用纳米液液滴对单个细胞的高度平行基因组表达分析。
影响因子：
64.5
作者：
Macosko EZ;Basu A;Satija R;Nemesh J;Shekhar K;Goldman M;Tirosh I;Bialas AR;Kamitaki N;Martersteck EM;Trombetta JJ;Weitz DA;Sanes JR;Shalek AK;Regev A;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
14.2
作者：
Barnes, Peter J.
通讯作者：
Barnes, Peter J.
影响因子：
12.3
作者：
Campbell JD;McDonough JE;Zeskind JE;Hackett TL;Pechkovsky DV;Brandsma CA;Suzuki M;Gosselink JV;Liu G;Alekseyev YO;Xiao J;Zhang X;Hayashi S;Cooper JD;Timens W;Postma DS;Knight DA;Lenburg ME;Hogg JC;Spira A
通讯作者：
Spira A