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. 2024 May 6:11:1369341.
doi: 10.3389/fmed.2024.1369341. eCollection 2024.

Single-cell transcriptome revealed dysregulated RNA-binding protein expression patterns and functions in human ankylosing spondylitis

Zheng Ren  1 , Chenyang Li #  2 , Jing Wang #  1 , Jiangtao Sui  1 , Yuan Ma  1
Affiliations

Single-cell transcriptome revealed dysregulated RNA-binding protein expression patterns and functions in human ankylosing spondylitis

Zheng Ren et al. Front Med (Lausanne). .

Abstract

Objective: To explore the expression characteristics and regulatory patterns of RBPs in different immune cell types of AS, and to clarify the potential key role of RBPs in the occurrence and development of AS disease.

Methods: PBMC sample data from scRNA-seq (HC*29, AS*10) and bulk RNA-seq (NC*3, AS*5) were selected for correlation analysis.

Results: (1) Compared with the HC group, the numbers of B, DC (dendritic cells), CD14+ Mono and CD8+ T cells were increased in AS group, while the numbers of platelet (platelets), CD8+ NKT, CD16+ Mono (non-classical monocytes), Native CD4+ T and NK were decreased. (2) Through the analysis of RBP genes in B cells, some RBPs were found to play an important role in B cell differentiation and function, such as DDX3X, SFPQ, SRRM1, UPF2. (3) It may be related to B-cell receptor, IgA immunity, NOD-like receptor and other signaling pathways; Through the analysis of RBP genes in CD8+ T cells, some RBPs that play an important role in the immune regulation of CD8+ T were found, such as EIF2S3, EIF4B, HSPA5, MSL3, PABPC1 and SRSF7; It may be related to T cell receptor, TNF, IL17 and other signaling pathways. (4) Based on bulk RNA-seq, it was found that compared with HC and AS patients, differentially expressed variable splicing genes (RASGs) may play an important role in the occurrence and development of AS by participating in transcriptional regulation, protein phosphorylation and ubiquitination, DNA replication, angiogenesis, intracellular signal transduction and other related pathways.

Conclusion: RBPs has specific expression characteristics in different immune cell types of AS patients, and has important regulatory functions. Its abnormal expression and regulation may be closely related to the occurrence and development of AS.

Keywords: Ankylosing Spondylitis(AS); B cells; CD8+ T cells; Gene; RNA-binding proteins (RBPs); Single-cell RNA sequencing (scRNA-seq).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
scRNA-seq analysis of human PBMC from healthy donors and AS patients identified distinct cell types. (A) Flow chart for analysis of the scRNA-seq and bulk RNA-seq. (B) UMAP plot of single-cell transcriptomic profiles from ankylosing spondylitis patients and healthy subjects. Colors indicate cell clusters along with annotations. (C) DEG heatmap. (D) Rank order based on decreasing values of the relative frequency ratio between two sample groups.
Figure 2
Figure 2
scRNA-seq analysis revealed dysregulated RBPs and their regulatory functions in B cells. (A) Bar graphs show the number of DEGs and DERBPs. (B) Bar plot showing the most enriched GO results of DERBPs. (C) Cytoscape shows the co-expression network comprising differentially expressed RBPs from B cells. Edges connect RBP-target gene pairs while nodes represent DEGs. RBPs are displayed in larger font size and deep purple color. (D) Gene ontology enrichment analysis of KEGG pathway of target genes for each RBP from graph (C).
Figure 3
Figure 3
scRNA-seq analysis revealed specific RBPs regulatory module in CD8+ T cells. (A) Bar graphs show the number of DEGs and DERBPs. (B) Bar plot showing the most enriched GO results of DERBPs. (C) Cytoscape shows the co-expression network comprising differentially expressed RBPs from CD8+ T cells. Edges connect RBP-target gene pairs while nodes represent DEGs. RBPs are displayed in larger font size and deep purple color. (D) Gene ontology enrichment analysis of KEGG pathway of target genes for each RBP from graph (C).
Figure 4
Figure 4
Integration with bulk RNA-seq reveals that extensive alternative splicing regulation in ankylosing spondylitis may be related to the abnormal regulation of RBPs. (A) The Veen shows the number of DERBPs between the DEG and DERBP of single cell. (B) Bar plot showing the most enriched GO results of DERBPs. (C) The Heatmap showing the splicing ratio of specific RAS (PSAR ≥ 50%) in the AS vs. NC group. (D) Bar plot showing the top 15 most enriched KEGG results of specific DERBP co-expressed by specific RAS. (E) Co-expression analysis of specific DERBP and specific RAS of key GO biological process results. Cutoffs of P-value ≤ 0.05 and Pearson coefficient ≥ 0.7 or ≤−0.7 were applied to identify the co-expression pairs. The network showing the co-expressed GO pathway for specific DERBP and specific RAS.
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Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This article was sponsored by the National Natural Science Foundation of China, project number: 82260446, 81360280, 81760411.