Year: 2024
Type: article
Abstract: BACKGROUND: Cerebrovascular injury is a common pathological feature of a spectrum of neurological disorders, including traumatic brain injury (TBI), stroke, Alzheimer's disease (AD), and aging. Vascular manifestations among these conditions are similar indeed, including the breakdown of the blood-brain barrier (BBB). However, whether there is a unique molecular mechanism underlying the vascular changes among these conditions remains elusive. METHOD: We performed single-cell RNA (scRNA-seq) sequencing and obtained 29,114 high-quality cells combined from ipsilateral hemispheres of WT C57BL/6J Sham mice and mTBI mice at day 1, 3 and 7. RESULT: Joint clustering of all groups revealed 7 cell populations using their specific genetic markers, including vEC, vcapEC, capEC, acapEC, aEC. Next, we identified differential expression genes between Sham and day 1 or day 3 or day 7 post-mTBI within each endothelial cell cluster. CONCLUSION: Based on transcriptomic analysis on cerebrovascular scRNA-seq datasets, we identified a common molecular signature between mTBI and aging vasculature, involving a novel transmembrane protein gene Tmem252. Tmem252 upregulation in brain endothelial cells may represent a shared endophenotype of microvascular injuries in different pathological conditions, and therapeutically targeted for treating BBB breakdown and vascular dysfunctions.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.092817
Authors: Shangzhou Xia, Zhen Zhao
Institution: University of Southern California
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
OpenAlex ID: W4406050689