Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing Data

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. The heterogeneity of the disease can be investigated via single-cell RNA sequencing (scRNA-seq) for its gap in the literature. Firstly, five types of immune cells (plasma cells, naive CD4 T cells, memory-ac...

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Main Authors: Wenbo Zhang, Zhe Cai, Dandan Liang, Jiaochan Han, Ping Wu, Jiayi Shan, Guangxun Meng, Huasong Zeng
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/13/10619
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author Wenbo Zhang
Zhe Cai
Dandan Liang
Jiaochan Han
Ping Wu
Jiayi Shan
Guangxun Meng
Huasong Zeng
author_facet Wenbo Zhang
Zhe Cai
Dandan Liang
Jiaochan Han
Ping Wu
Jiayi Shan
Guangxun Meng
Huasong Zeng
author_sort Wenbo Zhang
collection DOAJ
description Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. The heterogeneity of the disease can be investigated via single-cell RNA sequencing (scRNA-seq) for its gap in the literature. Firstly, five types of immune cells (plasma cells, naive CD4 T cells, memory-activated CD4 T cells, eosinophils, and neutrophils) were significantly different between normal control (NC) and JIA samples. WGCNA was performed to identify genes that exhibited the highest correlation to differential immune cells. Then, 168 differentially expressed immune cell-related genes (DE-ICRGs) were identified by overlapping 13,706 genes identified by WGCNA and 286 differentially expressed genes (DEGs) between JIA and NC specimens. Next, four key genes, namely <i>SOCS3</i>, <i>JUN</i>, <i>CLEC4C</i>, and <i>NFKBIA,</i> were identified by a protein–protein interaction (PPI) network and three machine learning algorithms. The results of functional enrichment revealed that <i>SOCS3</i>, <i>JUN</i>, and <i>NFKBIA</i> were all associated with hallmark TNF-α signaling via NF-κB. In addition, cells in JIA samples were clustered into four groups (B cell, monocyte, NK cell, and T cell groups) by single-cell data analysis. <i>CLEC4C</i> and <i>JUN</i> exhibited the highest level of expression in B cells; <i>NFKBIA</i> and <i>SOCS3</i> exhibited the highest level of expression in monocytes. Finally, real-time quantitative PCR (RT-qPCR) revealed that the expression of three key genes was consistent with that determined by differential analysis. Our study revealed four key genes with prognostic value for JIA. Our findings could have potential implications for JIA treatment and investigation.
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spelling doaj.art-60e6c638f98a4f6e85faab0f8627f4002023-11-18T16:41:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131061910.3390/ijms241310619Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing DataWenbo Zhang0Zhe Cai1Dandan Liang2Jiaochan Han3Ping Wu4Jiayi Shan5Guangxun Meng6Huasong Zeng7The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou 510623, ChinaDepartment of Allergy, Immunology and Rheumatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, ChinaThe First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaDepartment of Allergy, Immunology and Rheumatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, ChinaDepartment of Allergy, Immunology and Rheumatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, ChinaThe First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaThe Joint Center for Infection and Immunity, CAS Key Laboratory of Molecular Virology & Immunology, Chinese Academy of Sciences, Shanghai 200031, ChinaThe Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou 510623, ChinaJuvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. The heterogeneity of the disease can be investigated via single-cell RNA sequencing (scRNA-seq) for its gap in the literature. Firstly, five types of immune cells (plasma cells, naive CD4 T cells, memory-activated CD4 T cells, eosinophils, and neutrophils) were significantly different between normal control (NC) and JIA samples. WGCNA was performed to identify genes that exhibited the highest correlation to differential immune cells. Then, 168 differentially expressed immune cell-related genes (DE-ICRGs) were identified by overlapping 13,706 genes identified by WGCNA and 286 differentially expressed genes (DEGs) between JIA and NC specimens. Next, four key genes, namely <i>SOCS3</i>, <i>JUN</i>, <i>CLEC4C</i>, and <i>NFKBIA,</i> were identified by a protein–protein interaction (PPI) network and three machine learning algorithms. The results of functional enrichment revealed that <i>SOCS3</i>, <i>JUN</i>, and <i>NFKBIA</i> were all associated with hallmark TNF-α signaling via NF-κB. In addition, cells in JIA samples were clustered into four groups (B cell, monocyte, NK cell, and T cell groups) by single-cell data analysis. <i>CLEC4C</i> and <i>JUN</i> exhibited the highest level of expression in B cells; <i>NFKBIA</i> and <i>SOCS3</i> exhibited the highest level of expression in monocytes. Finally, real-time quantitative PCR (RT-qPCR) revealed that the expression of three key genes was consistent with that determined by differential analysis. Our study revealed four key genes with prognostic value for JIA. Our findings could have potential implications for JIA treatment and investigation.https://www.mdpi.com/1422-0067/24/13/10619juvenile idiopathic arthritisWGCNAprotein–protein interactionmachine learning analysissingle-cell RNA sequencing
spellingShingle Wenbo Zhang
Zhe Cai
Dandan Liang
Jiaochan Han
Ping Wu
Jiayi Shan
Guangxun Meng
Huasong Zeng
Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing Data
International Journal of Molecular Sciences
juvenile idiopathic arthritis
WGCNA
protein–protein interaction
machine learning analysis
single-cell RNA sequencing
title Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing Data
title_full Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing Data
title_fullStr Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing Data
title_full_unstemmed Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing Data
title_short Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing Data
title_sort immune cell related genes in juvenile idiopathic arthritis identified using transcriptomic and single cell sequencing data
topic juvenile idiopathic arthritis
WGCNA
protein–protein interaction
machine learning analysis
single-cell RNA sequencing
url https://www.mdpi.com/1422-0067/24/13/10619
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