scholarly journals Single-cell meta-analysis of cigarette smoking lung atlas

2021 ◽  
Author(s):  
Jun Nakayama ◽  
Yusuke Yamamoto

Single-cell RNA-seq (scRNA-seq) technologies have been broadly utilized to reveal the molecular mechanisms of respiratory diseases and physiology at single-cell resolution. Here, we constructed a cigarette smoking lung atlas by integrating data from 8 public datasets, including 104 lung scRNA-seq samples with patient state information. The cigarette smoking lung atlas generated by this single-cell meta-analysis (scMeta-analysis) revealed early carcinogenesis events and defined the alterations of single-cell gene expression, cell population, fundamental properties of biological pathways, and cell-cell interactions induced by cigarette smoking. In addition, we developed two novel scMeta-analysis methods incorporating clinical metadata: VARIED (Visualized Algorithms of Relationships In Expressional Diversity) and AGED (Aging-related Gene Expressional Differences). VARIED analysis revealed the expressional diversity associated with smoking carcinogenesis in each cell population. AGED analysis revealed differences in gene expression related to both aging and smoking states. Our scMeta-analysis provided new insights into the effects of smoking and into cellular diversity in the human lung at single-cell resolution.

2010 ◽  
Vol 18 (4) ◽  
pp. 675-685 ◽  
Author(s):  
Guoji Guo ◽  
Mikael Huss ◽  
Guo Qing Tong ◽  
Chaoyang Wang ◽  
Li Li Sun ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yong Zhong ◽  
Xiangcheng Xiao

Abstract Background and Aims The exact molecular mechanisms underlying IgA nephropathy (IgAN) remains incompletely defined. Therefore, it is necessary to further elucidate the mechanism of IgA nephropathy and find novel therapeutic targets. Method Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from 4 IgAN and 1 control subjects to define the transcriptomic landscape at the single-cell resolution. Unsupervised clustering analysis of kidney specimens was used to identify distinct cell clusters. Differentially expressed genes and potential signaling pathways involved in IgAN were also identified. Results Our analysis identified 14 cell subsets in kidney biopsies from IgAN patients, and analyzed changing gene expression in distinct renal cell types. We found increased mesangial expression of several novel genes including MALAT1, GADD45B, SOX4 and EDIL3, which were related to proliferation and matrix accumulation and have not been reported in IgAN previously. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling and NOD-like receptor signaling. Moreover, the receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. Specifically, IgAN with overt proteinuria displayed elevated genes participating in several signaling pathways which may be involved in pathogenesis of progression of IgAN. Conclusion The comprehensive analysis of kidney biopsy specimen demonstrated different gene expression profile, potential pathologic ligand-receptor crosstalk, signaling pathways in human IgAN. These results offer new insight into pathogenesis and identify new therapeutic targets for patients with IgA nephropathy.


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