Integrated analysis of scRNA-seq and TCR-seq on T cells in aneurysmal subarachnoid hemorrhage: A descriptive, hypothesis-generating case study

This studthe transcriptomic profiles and T cell receptor (TCR) repertoires of T cells in paired cerebrospinal fluid (CSF) and peripheral blood (PB) from 2 patients with aneurysmal subarachnoid hemorrhage (SAH). This descriptive work primarily generates research hypotheses and does not explore causal biological mechanisms. Single-cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq) were performed on T cells isolated from CSF and PB samples collected on day 7 post-onset from 2 male patients. A series of descriptive analyses were conducted, including T cell subset classification, pseudotime trajectory reconstruction, pathway enrichment, CellChat-based cell-cell communication analysis, and TCR clonality assessment. Public scRNA-seq data of CSF samples from 8 healthy individuals were downloaded from the Gene Expression Omnibus database and used as external healthy controls. A total of 6058 T cells for scRNA-seq and 5008 T cells for TCR-seq were analyzed in this study. Five distinct T cell subsets were observed. In these 2 patients, CSF-derived T cells showed stronger signaling pathway activation and increased clonal expansion than PB-derived T cells. Compared with healthy controls from the public dataset, T cells from SAH patients presented enhanced signaling pathway activity and more extensive cell-cell interactions. All above observations are limited to these 2 individuals and cannot be generalized to all SAH patients without large independent cohort validation. This descriptive case-based study establishes a high-resolution single-cell atlas of T cells from 2 SAH patients. The observed differences between CSF and PB, as well as between SAH patients and healthy controls, provide directions for future mechanistic investigations.