Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov
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Abstract
In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed five large-scale bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression and its distribution among cell types. We didn’t find significant disparities in ACE2 gene expression between racial groups (Asian vs Caucasian), age groups (>60 vs <60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in former smoker’s lung compared to non-smoker’s lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.
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SciScore for 10.1101/2020.02.05.20020107: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Bulk transcriptomics: Two RNA-seq datasets and two DNA microarray datasets from lung cancer patients were analyzed in this study, including a Caucasian RNA-seq dataset from TCGA (https://www.cancer.gov/tcga), an Asian RNA-seq dataset from Gene Expression Omnibus (GEO) with the accession number GSE404196, an Asian microarray dataset from GEO with the accession number GSE198047 and a Caucasian microarray dataset from GEO with the accession number GSE100728. Gene Expression OmnibusSciScore for 10.1101/2020.02.05.20020107: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Bulk transcriptomics: Two RNA-seq datasets and two DNA microarray datasets from lung cancer patients were analyzed in this study, including a Caucasian RNA-seq dataset from TCGA (https://www.cancer.gov/tcga), an Asian RNA-seq dataset from Gene Expression Omnibus (GEO) with the accession number GSE404196, an Asian microarray dataset from GEO with the accession number GSE198047 and a Caucasian microarray dataset from GEO with the accession number GSE100728. Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)Counts of single cells were downloaded, and subsequent data analyses were performed using the Seurat 3.0 package15, including data normalization, high variable feature selection, data scaling, dimension reduction and cluster identification. Seuratsuggested: (SEURAT, RRID:SCR_007322)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:One limitation of this study is that the small sample size of current single-cell transcriptome datasets has limited power in studying multiple factors involved in this question. Whether ACE2 is the only or major receptor of 2019-nCov is unknown. The reason(s) for the tobacco-related disparity in ACE2 expression is unknown. Studies found smoke significantly increased ACE2 expression in the lung of rats20 and cigarette smoke exposure increased pulmonary ACE2 activities in mice21. Controversially, other studies showed chronic cigarette smoke and nicotine decreased ACE2 expression in rats22,23. Thus, substance other than nicotine might contribute to the smoking-related upregulation of ACE2 found in this study. Further studies are required to find the answer. Despites current limited knowledge, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen. Wuhan, stay strong. Ethical oversight: There is no direct involvement of human subjects in this study. All the data use existing de-identified biological samples and data from prior studies. Therefore, ethical oversight and patient consent were not handled in this project.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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