Integrated single-cell multiomics reveals novel immune candidate markers for post-traumatic coagulopathy

Abstract

Introduction: Post-traumatic coagulopathy (PTC) is a critical pathology in traumatic brain injury (TBI), however, its potential mechanism is not clear. To explore this in peripheral samples, we integrated single cell RNA-sequencing and T cell repertoire (TCR)-sequencing across a cohort of patients with TBI.

Methods: Clinical samples from patients with more brain severity demonstrated overexpression of T cell receptor-encoding genes and less TCR diversity.

Results: By mapping TCR clonality, we found patients with PTC have less TCR clones, and the TCR clones are mainly distributed in cytotoxic effector CD8+T cell. In addition, the counts of CD8+ T cell and natural killer (NK) cells are associated with the coagulation parameter by WGCNA, and the granzyme and lectin-like receptor profiles are also decreased in the peripheral blood from TBI patients, suggesting that reduced peripheral CD8+ clonality and cytotoxic profiles may be involved in PTC after TBI.

Conclusion: Our work systematically revealed the critical immune status in PTC patients at the single-cell level.

Keywords: RNA-seq; TCR-seq; multi-omics; post-traumatic coagulopathy; single-cell.