# Unveiling the molecular mechanisms of burn injury through integrated single-cell and bulk transcriptomic analysis

**Authors:** Xiaoyu Zhu, Neng Huang, Yanyan Pan, Xin Le, Shengyong Cui, Jiliang Li, Youfen Fan

PMC · DOI: 10.1371/journal.pone.0341725 · 2026-01-27

## TL;DR

This study uses advanced sequencing to explore how different cells and genes interact in burn injuries, aiming to improve treatments.

## Contribution

The study identifies key genes and cell interactions in burn injuries using single-cell RNA sequencing and machine learning.

## Key findings

- Macrophages were found to play a central role in immune signaling in burn injuries.
- 155 marker genes were identified for Macrophages, including AP2A2, CCL7, and TF.
- Mast cells and Neutrophils showed significant involvement in disease progression.

## Abstract

Burn injuries are prevalent and have a significant effect on patients’ quality of life and healthcare costs. Current treatment modalities, such as wound care and surgical interventions, often face challenges due to complications like infection and inadequate healing.

This study adopted single-cell RNA sequencing (scRNA-seq) to investigate the cellular landscape of the burn microenvironment. After rigorous quality control filtering, 9,248 cells were retained for analysis. Using UMAP dimensionality reduction, these cells were annotated into 14 subpopulations, including Neutrophils, Macrophages, and T cells. Differential gene analysis and machine learning techniques, such as LASSO regression and random forest selection, were employed to identify marker genes.

Macrophages exhibited significant interactions with other cell types, indicating their pivotal role in immune signaling within the burn microenvironment. A total of 155 genes were identified as markers for Macrophages, with AP2A2, CCL7, and TF emerging as key features. Immune infiltration analysis also revealed notable differences in the proportions of immune cells, particularly Mast cells and Neutrophils, highlighting on their involvement in disease progression.

This study provides novel insights into the immunological microenvironment of burn injuries. Despite limitations including a modest sample size and lack of experimental validation, our findings establish a foundation for future investigations into targeted immunotherapeutic strategies, potentially improving clinical outcomes and advancing personalized treatment approaches for burn patients.

## Linked entities

- **Genes:** AP2A2 (adaptor related protein complex 2 subunit alpha 2) [NCBI Gene 161], CCL7 (C-C motif chemokine ligand 7) [NCBI Gene 6354], TF (transferrin) [NCBI Gene 7018]

## Full-text entities

- **Genes:** CCL7 (C-C motif chemokine ligand 7) [NCBI Gene 6354] {aka FIC, MARC, MCP-3, MCP3, NC28, SCYA6}, AP2A2 (adaptor related protein complex 2 subunit alpha 2) [NCBI Gene 161] {aka ADTAB, CLAPA2, HIP-9, HIP9, HYPJ}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}
- **Diseases:** infection (MESH:D007239), Burn injuries (MESH:D002056)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12843517/full.md

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Source: https://tomesphere.com/paper/PMC12843517