Single-cell RNA Sequencing Reveals Evolution of Immune Landscape in Perihematomal Edema Post Hemorrhagic Stroke

Research Background

Intracerebral hemorrhage (ICH) is one of the global health threats, renowned for its high disability and mortality rates. Among the secondary brain injuries caused by ICH, the formation of perihematomal edema (PHE) is a significant factor for its lethality. However, the exact pathophysiological mechanisms behind PHE are not fully understood. This study aims to detail the transcription profiles of immune cell populations in human PHE tissues and explore microscopic-level differences in various types of immune cells.

Source of the Paper

The paper, co-written by Peng Zhang, Cong Gao, and others, with Daojing Li as the corresponding author, comes from the Affiliated Hospital of Jining Medical University. It was published in the Journal of Neuroinflammation in 2024, with the DOI being 10.1186/s12974-024-03113-8.

Research Methods and Procedures

The study included a total of 9 basal ganglia ICH patients. Based on the different time periods post-ICH, they were divided into three groups: Group G1 (0-6h), Group G2 (6-24h), and Group G3 (24-48h), with 3 patients in each group. Edema tissues around the hematoma were retained during hematoma clearance. Single-cell RNA sequencing (scRNA-seq) was used to map the immune cell populations in the PHE samples from patients at different stages. Additionally, various bioinformatics analysis methods were employed, such as Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), Single-cell Regulatory Network Inferencing and Clustering (SCENIC) analysis, Monocle2 pseudotime analysis, and cell-cell communication analysis.

Major Research Results

For the first time, the study established a comprehensive map of diverse immune cell populations within human PHE tissue at the single-cell level, identifying 12 microglia subpopulations and 5 neutrophil subpopulations. The study found that the Secreted Phosphoprotein 1 (SPP1) pathway is fundamental for self-communication among microglial subpopulations during PHE progression and traced the trajectory branches of different neutrophil subtypes. Furthermore, it was demonstrated that osteopontin (OPN) produced by microglia can regulate the immune environment within PHE tissue through interactions with CD44-positive cells.

Research Conclusions and Significance

The study provides valuable insights into the immune microenvironment within PHE tissue, with potential applications in the development of new therapeutic approaches for ICH. The findings not only shed light on the issues at hand but also contribute to the innovation of research methods and workflows, as well as the uniqueness of the research subjects.

Limitations of the Study

The sample size of the study is relatively small and exclusively from the Asian population, which may limit the generalizability of the findings. Additionally, immunofluorescence staining was only performed in ICH patient samples without comparison to a control group, which may limit the credibility of the validation results.