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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Inflammation

This article is part of the Research TopicNew Insights into Immunity in Musculoskeletal Disorders: Focusing on Bone, Joint, and Soft Tissue PathologiesView all 9 articles

Combination of single-cell and bulk RNA-seq reveals changes in immune landscape in osteomyelitis

Provisionally accepted
  • Wuhan Fourth Hospital, Wuhan, China

The final, formatted version of the article will be published soon.

Objective: This study presented a comprehensive characterization of the osteomyelitis immune microenvironment, identified driver genes and pathogenic cell populations underlying disease progression, and uncovered potential therapeutic targets through single-cell and bulk transcriptomic analysis. Methods: We analyzed time-series transcriptomic sequencing data from mouse osteomyelitis samples in dataset GSE168896. Fuzzy c-means clustering was applied to reveal gene sets linked to disease progression. Immune cell infiltration analysis was conducted through online tool ImmuCellAI-mouse. Furthermore, by leveraging single-cell sequencing data, we characterized immune cell subpopulations and pinpointed the key cell subtypes that exhibited in osteomyelitis mouse. Results: We identified six gene clusters exhibiting distinct temporal expression patterns and functional roles in osteomyelitis, such as leukocyte and lymphocyte activation, ossification. Single-cell sequencing analysis further showed 7 distinct cellular subpopulations. Among these, macrophages demonstrated a significant increase following osteomyelitis, and the infiltration of Mif+Cd63+, Arg1+Sdc4+ and Cxcl1+Ccl4+ macrophages significantly increased. Besides, Ccl3-Ccr1 and Cxcl2-Cxcr2 ligand-receptors contributed mostly in immune cells. Conclusion: Our findings tracked the transcriptional dynamics and evolving immune landscape of osteomyelitis, highlighting macrophages as central regulators of disease progression. We identified the significant infiltration of Arg1+Sdc4+, Cxcl1+Ccl4+ and Mif+Cd63+macrophages may affect osteomyelitis through the Ccl3-Ccr1 and Cxcl2-Cxcr2 signaling pathways. These findings offer a new perspective on immune regulation in osteomyelitis.

Keywords: Gene Expression, Immune Cell Infiltration, Macrophages, Osteomyelitis, single-cell sequencing, therapeutic targets, Transcriptomic Analysis

Received: 14 Nov 2025; Accepted: 13 Feb 2026.

Copyright: © 2026 Zhu, Jing, Chen, Tan, Zeng and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Jie Tan
Ji Zeng
Zheng Jin

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