Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD

转录组 慢性阻塞性肺病 生物 基因 电池类型 细胞 基因表达谱 基因表达 基因签名 遗传学 医学 内科学
作者
Xiuying Li,Guillaume Noell,Tracy Tabib,Alyssa D. Gregory,Humberto E. Trejo Bittar,Ravi Vats,Tomasz W. Kaminski,John Sembrat,Mark E. Snyder,Divay Chandra,Kong Chen,Chunbin Zou,Yingze Zhang,Prithu Sundd,John F. McDyer,Frank C. Sciurba,Mauricio Rojas,Robert Lafyatis,Steve D. Shapiro,Rosa Faner,Toru Nyunoya
出处
期刊:Respiratory Research [BioMed Central]
卷期号:22 (1) 被引量:12
标识
DOI:10.1186/s12931-021-01675-2
摘要

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.
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