Single-Cell RNA Sequencing and Transcriptome Analysis Revealed the Immune Microenvironment and Gene Markers of Acute Respiratory Distress Syndrome

Abstract

Dan He,1,* Qiao Yu,2,* Xiaona Zeng,2,* Jihua Feng,2 Ruiqi Yang,2 Huan Wan,2 Ying Zhong,2 Yanli Yang,2 Ruzhi Zhao,2 Junyu Lu,3,4 Jianfeng Zhang1,2,4 1Department of General Practice, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China; 2Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China; 3Intensive Care Unit, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China; 4Guangxi Health Commission Key Laboratory of Emergency and Critical Medicine, Nanning, 530007, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianfeng Zhang, Junyu Lu, The Second Affiliated Hospital of Guangxi Medical University, No. 166 Daxuedong Road, Nanning, Guangxi, 530007, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]; [email protected]: Acute respiratory distress syndrome (ARDS) is caused by severe pulmonary inflammation and the leading cause of death in the intensive care unit.Methods: We used single-cell RNA sequencing to compare peripheral blood mononuclear cells from sepsis-induced ARDS (SEP-ARDS) and pneumonic ARDS (PNE-ARDS) patient. Then, we used the GSE152978 and GSE152979 datasets to identify molecular dysregulation mechanisms at the transcriptional level in ARDS.Results: Markedly increased CD14 cells were the predominant immune cell type observed in SEP-ARDS and PNE-ARDS patients. Cytotoxic cells and natural killer (NK) T cells were exclusively identified in patients with PNE-ARDS. An enrichment analysis of differentially expressed genes (DEGs) suggested that Th1 cell differentiation and Th2 cell differentiation were enriched in cytotoxic cells, and that the IL-17 signaling pathway, NOD receptor signaling pathway, and complement and coagulation cascades were enriched in CD14 cells. Furthermore, according to GSE152978 and GSE152979, 1939 DEGs were identified in patients with ARDS and controls; they were mainly enriched in the Kyoto Encyclopedia of Genes and Genomes pathways. RBP7 had the highest area under the curve values among the 12 hub genes and was mainly expressed in CD14 cells. Additionally, hub genes were negatively correlated with NK cells and positively correlated with neutrophils, cytotoxic cells, B cells, and macrophages.Conclusion: A severe imbalance in the proportion of immune cells and immune dysfunction were observed in SEP-ARDS and PNE-ARDS patients. RBP7 may be immunologically associated with CD14 cells and serve as a potential marker of ARDS.Keywords: acute respiratory distress syndrome, single-cell RNA sequencing, biomarker, immune disorders, differentially expressed genes

Keywords

• acute respiratory distress syndrome
• single-cell rna sequencing
• biomarker
• immune disorders
• differentially expressed genes