Single-cell sequencing-based study of ferroptosis mechanisms in heat stroke: identification of key biomarkers and dynamic analysis of the immune microenvironment

作者：Defeng Yin, Qin Guo, Hao Jiang, Yiqiang Hu, Yonglan Hu, Xiang Li, Xiang Li, Chenglin Wang, Shilin Li, Kaiyu Jin, Yingchun Hu, Yingchun Hu · 发表于：BMC Medical Genomics · 年份：2025 · DOI：10.1186/s12920-025-02188-3 · 被引用次数：11 · 研究领域：Climate Change and Health Impacts、Cancer-related molecular mechanisms research、Adipose Tissue and Metabolism

BACKGROUND: Heat stroke, caused by excessive heat production or impaired dissipation, often results from prolonged heat exposure or strenuous activity. Ferroptosis, a novel form of programmed cell death, has been implicated in its pathogenesis, though its mechanisms remain unclear. OBJECTIVE: This study investigates the molecular mechanisms linking heat stroke and ferroptosis using single-cell and transcriptomic analyses to identify diagnostic and therapeutic targets. METHODS: Peripheral blood samples from 29 heat stroke patients, recruited at an early stage of the condition, underwent transcriptome sequencing, and single-cell RNA sequencing was conducted for two representative cases. Ferroptosis-related genes were identified by integrating the FerrDB database, followed by weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis to pinpoint ferroptosis-related genes most characteristic of heat stroke. Functional enrichment analyses, including GO and KEGG pathways, were performed. Single-cell RNA sequencing revealed immune microenvironment alterations and marker genes linked to heat stroke pathogenesis. Receiver operating characteristic (ROC) analysis evaluated the diagnostic potential of these genes. Additionally, pseudotime analysis elucidated cell differentiation trajectories and the roles of key genes. RESULTS: In Dataset 1, 630 differentially expressed genes (546 up-regulated, 84 down-regulated) and 1,979 heat stroke-related genes wer...