Dataset Information

Single-cell RNA-seq data analysis characterizing bronchoalveolar epithelial cells in patients with SARS-CoV-2 infection.

ABSTRACT:

Background

Angiotensin-converting enzyme 2 (ACE2) has been reported to be the main receptor for SARS-CoV-2 infection of host cells. Understanding the changes in bronchoalveolar epithelial cells after SARS-CoV-2 infection of host cells and the intercellular communication relationship between these epithelial cell changes and immune cells is of great significance for the development of therapeutic methods.

Methods

We explored the single-cell RNA sequence (scRNA-seq) of cells infected with bronchoalveolar lavage fluid (BaLF) of patients with different severities of SARS-CoV-2 and healthy people.

Results

We found 11 clusters of epithelial cells in the BaLF, and they were derived from the S group. In the S group, the proportion of cells with positive ACE2 expression was relatively high. ACE2 was relatively more expressed in epithelial cell clusters 1, 3, and 7. Clusters 4 and 5 represented the original state, and there were two differentiation directions: one was cluster 2, and the others were clusters 1, 3, and 6. Cluster 7 was the intermediate state. Clusters 1, 3, 6, and 7 had high similarities (> 0.9), and their main signaling pathways focused on inflammatory activation and immune response. Cluster 2 was relatively specific and was up-regulated in differential genes that were mainly related to apoptosis. The ligand-receptor expression pattern of TNFRSF10D-TNFSF10 showed a special inter-cell regulatory relationship between epithelial cell cluster 2 and macrophages.

Conclusion

This study revealed the changes in epithelial cells derived from alveolar lavage fluid after SARS-CoV-2 infection and the communication relationship with other immune cells.

SUBMITTER: Deng Z

PROVIDER: S-EPMC9441843 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Single-cell RNA-seq data analysis characterizing bronchoalveolar epithelial cells in patients with SARS-CoV-2 infection.

Deng Zhiqin Z Li Qin Q Li Yongshen Y Deng Zhenhan Z Chen Xiaoqiang X Zhao Zhe Z Wang Guganghui G Wang Daping D Liu Jianquan J Li Wencui W

Journal of inflammation (London, England) 20220905 1

<h4>Background</h4>Angiotensin-converting enzyme 2 (ACE2) has been reported to be the main receptor for SARS-CoV-2 infection of host cells. Understanding the changes in bronchoalveolar epithelial cells after SARS-CoV-2 infection of host cells and the intercellular communication relationship between these epithelial cell changes and immune cells is of great significance for the development of therapeutic methods.<h4>Methods</h4>We explored the single-cell RNA sequence (scRNA-seq) of cells infecte ...[more]

PMID: 36064702

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Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 19 (COVID-19) that was emerged as a new member of coronaviruses since December 2019 in Wuhan, China and then after was spread in all continentals. Since SARS-CoV-2 has shown about 77.5% similarity to SARS-CoV, the transcriptome and immunological regulations of SARS-CoV-2 was expected to have high percentage of overlap with SARS-CoV.ResultsIn this study, we applied the single cell transcriptomics data of human bronchial epithelial cells (2B4 cell line) infected with SARS-CoV, which was annotated in the Expression Atlas database to expand this data to COVID-19. In addition, we employed system biology methods including gene ontology (GO) and Reactome pathway analyses to define functional genes and pathways in the infected cells with SARS-CoV. The transcriptomics analysis on the Expression Atlas database revealed that most genes from infected 2B4 cell line with SARS-CoV were downregulated leading to immune system hyperactivation, induction of signaling pathways, and consequently a cytokine storm. In addition, GO:0016192 (vesicle-mediated transport), GO:0006886 (intracellular protein transport), and GO:0006888 (ER to Golgi vesicle-mediated transport) were shown as top three GOs in the ontology network of infected cells with SARS-CoV. Meanwhile, R-HAS-6807070 (phosphatase and tensin homolog or PTEN regulation) showed the highest association with other Reactome pathways in the network of infected cells with SARS-CoV. PTEN plays a critical role in the activation of dendritic cells, B- and T-cells, and secretion of proinflammatory cytokines, which cooperates with downregulated genes in the promotion of cytokine storm in the COVID-19 patients.ConclusionsBased on the high similarity percentage of the transcriptome of SARS-CoV with SARS-CoV-2, the data of immunological regulations, signaling pathways, and proinflammatory cytokines in SARS-CoV infection can be expanded to COVID-19 to have a valid platform for future pharmaceutical and vaccine studies.

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious and pathogenic coronavirus that emerged in late 2019 and caused a pandemic of respiratory illness termed as coronavirus disease 2019 (COVID-19). Cancer patients are more susceptible to SARS-CoV-2 infection. The treatment of cancer patients infected with SARS-CoV-2 is more complicated, and the patients are at risk of poor prognosis compared to other populations. Patients infected with SARS-CoV-2 are prone to rapid development of acute respiratory distress syndrome (ARDS) of which pulmonary fibrosis (PF) is considered a sequelae. Both ARDS and PF are factors that contribute to poor prognosis in COVID-19 patients. However, the molecular mechanisms among COVID-19, ARDS and PF in COVID-19 patients with cancer are not well-understood. In this study, the common differentially expressed genes (DEGs) between COVID-19 patients with and without cancer were identified. Based on the common DEGs, a series of analyses were performed, including Gene Ontology (GO) and pathway analysis, protein-protein interaction (PPI) network construction and hub gene extraction, transcription factor (TF)-DEG regulatory network construction, TF-DEG-miRNA coregulatory network construction and drug molecule identification. The candidate drug molecules (e.g., Tamibarotene CTD 00002527) obtained by this study might be helpful for effective therapeutic targets in COVID-19 patients with cancer. In addition, the common DEGs among ARDS, PF and COVID-19 patients with and without cancer are TNFSF10 and IFITM2. These two genes may serve as potential therapeutic targets in the treatment of COVID-19 patients with cancer. Changes in the expression levels of TNFSF10 and IFITM2 in CD14+/CD16+ monocytes may affect the immune response of COVID-19 patients. Specifically, changes in the expression level of TNFSF10 in monocytes can be considered as an immune signature in COVID-19 patients with hematologic cancer. Targeting N6-methyladenosine (m6A) pathways (e.g., METTL3/SERPINA1 axis) to restrict SARS-CoV-2 reproduction has therapeutic potential for COVID-19 patients.

Dataset Information

Single-cell RNA-seq data analysis characterizing bronchoalveolar epithelial cells in patients with SARS-CoV-2 infection.

Background

Methods

Results

Conclusion

Publications

Single-cell RNA-seq data analysis characterizing bronchoalveolar epithelial cells in patients with SARS-CoV-2 infection.

Similar Datasets

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