Discovery of Endothelial–Monocyte Crosstalk in Ischemic‐Reperfusion Injury Following Liver Transplantation Based on Integration of Single‐Cell RNA and Transcriptome RNA Sequencing

作者：Chao Sun, Li Li, Dan Li, Zhengxin Wang · 发表于：Journal of Cellular and Molecular Medicine · 年份：2025 · DOI：10.1111/jcmm.70336 · 被引用次数：6 · 研究领域：Immune cells in cancer、MicroRNA in disease regulation、Organ Transplantation Techniques and Outcomes

Hepatic ischemia/reperfusion injury (IRI) commonly complicates liver transplantation (LT). However, the precise mechanisms underlying hepatic IRI remain incompletely understood. We acquired single-cell RNA sequencing (scRNA-seq) and transcriptome RNA sequencing data of LT patients from the GEO database. Employing scRNA-seq, we delved into the interplay between non-immune and immune cells in hepatic IRI, pinpointing genes exhibiting altered expression patterns. Integrating insights gleaned from scRNA-seq and transcriptome RNA sequencing datasets, we deepened our comprehension of cellular interactions and underlying mechanisms in hepatic IRI. Additionally, we conducted preliminary validation of identified gene expression alterations using immunofluorescence techniques. Using scRNA-seq, we detected significant changes in the populations of liver sinusoidal endothelial cells (LSECs) and monocytes after hepatic ischemia-reperfusion injury (IRI). By integrating scRNA-seq with bulk transcriptome RNA sequencing data, we identified key genes with dysregulated expression in LSECs (ICAM1, SOCS3, NFKBIZ, JUND, TNFRSF12A and HSPA6) and monocytes (SOCS3, JUND, FPR2 and NR4A2). Our analysis of cell communication indicated that the ANXA1-FPR2 axis might be a pivotal signature in mediating interactions between LSECs and monocytes. We then established a mouse model for IRI, and further analyses using flow cytometry and immunofluorescence showed a significant increase in monocyte proportion pos...