Single-Cell Profiling Resolved Transcriptional Alterations and Lineage Dynamics of Subventricular Zone after Mild Traumatic Brain Injury

Abstract

Mild traumatic brain injury (mTBI) is the most common form of brain trauma caused by physical impact. The subventricular zone (SVZ) is a neurogenetic niche that contributes to homeostasis and repair after brain injury. It is particularly challenging to fully elucidate the molecular alterations in the SVZ occurring in response to injury due to its cell diversity and the complex network. In this study, we aimed to address this issue using a novel transcriptomic technique- unbiased single-cell RNA sequencing. We resolved previous unknown cell subpopulations harbored in the niche, and uncovered cell type-specific alterations in gene expression, enriched pathways, and cell-cell crosstalk following mTBI. Notably, we also report novel lineage trajectories and molecular hallmarks that govern neurogenesis. This study dissects the delicate transcriptome changes of individual cell types as well as the reprogramming process of cells in the SVZ niche after mTBI, and our findings are expected to facilitate the development of therapeutic interventions or diagnostic tests for mTBI.

Neural stem cells isolated from activated brain neurogenic niches after traumatic injury demonstrate distinct behaviorsin vitro

“…Such a pattern may reflect a TBI-induced alteration in NSC behavior, potentially stemming from lesion-induced cell type-specific changes in gene expression and lineage trajectory within the SVZ-derived NSC population. This aligns with prior findings indicating the unique response of the SVZ neurogenic niche to traumatic brain injury (Chen et al 2021, Yoshiya et al 2003).…”