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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Single-cell RNA-sequencing combined with bulk RNA-sequencing analysis of peripheral blood reveals the characteristics and key immune cell genes of ulcerative colitis
Yan-Cheng Dai, Dan Qiao, Chen-Ye Fang, Qiu-Qin Chen, Ren-Ye Que, Tie-Gang Xiao, Lie Zheng, Li-Juan Wang, Ya-Li Zhang
Yan-Cheng Dai, Dan Qiao, Ren-Ye Que, Tie-Gang Xiao, Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
Chen-Ye Fang, Department of Gastroenterology, Traditional Chinese Medicine Hospital of Ningbo, Ningbo 315000, Zhejiang Province, China
Qiu-Qin Chen, Department of Pathology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
Lie Zheng, Department of Gastroenterology, Traditional Chinese Medicine Hospital of Xi’an 730000, Shaanxi Province, China
Li-Juan Wang, Experimental Education Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Ya-Li Zhang, Institute of Digestive Diseases, LongHua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Author contributions: Dai YC and Qiao D contributed equally to this work, and both implemented the software, conducted the simulations, analyzed the data, and wrote the manuscript; Fang CY, Chen QQ, and Que RY prepared the figures and tables; Xiao TG and Zheng L modified and reviewed the manuscript; Wang LJ, and Zhang YL conceived and supervised the study; all authors contributed to the article and approved the submitted version.
Supported by the National Natural Science Foundation of China, No. 81873253 and 81704009; the Shanghai Natural Science Foundation, No. 22ZR1458800, the Hongkou District Health Committee, No. HKZK2020A01 and the Xinglin Scholar Program of Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine 2020 Document No. 23.
Institutional review board statement: Since this article is a molecular mechanism study of network pharmacology and does not involve animal experiments or clinical experiments, it does not require the approval of an ethics committee.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Ya-Li Zhang, PhD, Research Fellow, Institute of Digestive Diseases, LongHua Hospital Shanghai University of Traditional Chinese Medicine, No. 725 South Wanping Road, Shanghai 200032, China.
zhanghappy181015@126.com
Received: July 26, 2022
Peer-review started: July 26, 2022
First decision: September 26, 2022
Revised: September 27, 2022
Accepted: October 27, 2022
Article in press: October 27, 2022
Published online: November 26, 2022
Processing time: 119 Days and 21.4 Hours
BACKGROUND
Ulcerative colitis (UC) is a complicated disease caused by the interaction between genetic and environmental factors that affects mucosal homeostasis and triggers an inappropriate immune response. Single-cell RNA sequencing (scRNA-seq) can be used to rapidly obtain the precise gene expression patterns of thousands of cells in the intestine, analyze the characteristics of cells with the same phenotype, and provide new insights into the growth and development of intestinal organs, the clonal evolution of cells, and immune cell changes. These findings can provide new ideas for the diagnosis and treatment of intestinal diseases.
AIM
To identify clinical phenotypes and biomarkers that can predict the response of UC patients to specific therapeutic drugs and thus aid the diagnosis and treatment of UC.
METHODS
Using the Gene Expression Omnibus (GEO) database, we analyzed peripheral blood cell subtypes of patients with UC by scRNA-seq combined with bulk RNA sequencing (RNA-seq) to reveal the core genes of UC. We then combined weighted gene correlation network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) analysis to reveal diagnostic markers of UC.
RESULTS
After processing the scRNA-seq data, we obtained data from approximately 24340 cells and identified 17 cell types. Through intercellular communication analysis, we selected monocyte marker genes as the candidate gene set for the prediction model. Construction of a WGCNA coexpression network identified RhoB, cathepsin D (CTSD) and zyxin (ZYX) as core genes. Immune infiltration analysis showed that these three core genes were strongly correlated with immune cells. Functional enrichment analysis showed that the differentially expressed genes were closely related to immune and inflammatory responses, which are associated with many challenges in the diagnosis and treatment of UC.
CONCLUSION
Through scRNA-seq analysis, LASSO diagnostic model building and WGCNA, we identified RhoB, CTSD and ZYX as core genes of UC that are closely related to monocyte infiltration that may serve as diagnostic markers and molecular targets for UC therapeutic intervention.
Core Tip: Using the Gene Expression Omnibus database, we analyzed peripheral blood cell subtypes of patients with ulcerative colitis (UC) by single-cell RNA sequencing (scRNA-seq) combined with bulk RNA sequencing (RNA-seq) to reveal the core genes of UC. Through scRNA-seq analysis, least absolute shrinkage and selection operator diagnostic model building and weighted gene correlation network analysis, we identified RhoB, cathepsin D and zyxin as core genes of UC that are closely related to monocyte infiltration that may serve as diagnostic markers and molecular targets for UC therapeutic intervention.
