Abstract WP66: Astrocyte, Oligodendrocyte, and OPC Response in the Human Brain After Stroke: A Single-Cell RNA Sequencing Study

• DOI: 10.1161/str.56.suppl_1.wp66
• Publication Date: 2025-01-30T10:26:41Z
• Authors: Chengcheng Zhao; Yao Xiuhua; Ma Yilin; Yue Zhang; Tao Chen; Cai Ying; jieli chen; JIALING WU
• Keywords: Stroke; Human brain

Introduction: Ischemic stroke (IS) significantly alters brain cellular composition and gene expression, particularly in glial cells like astrocytes (ASTs), oligodendrocytes (OLs), oligodendrocyte precursor (OPCs). While these cells' roles neural repair are recognized, the precise molecular mechanisms remain unclear. This study aims to elucidate IS-induced transcriptomic changes ASTs, OLs, OPCs using single-cell RNA sequencing (scRNA-seq) of human tissues. We hypothesize that IS triggers distinct alterations cells, crucial for post-stroke repair, which can be mapped specific subclusters with unique functions. Methods: performed scRNA-seq on five tissue samples: three controls from craniocerebral trauma patients two patients. Tissues were collected frontotemporal regions within 48 hours onset. analyzed 23,638 identifying eight cell types. Differential subcluster analysis, trajectory analysis focused explore functional implications observed changes. Results: resulted a marked increase ASTs OPCs, while OLs decreased number. displayed significant transcriptional alterations, associated synaptic signaling axon development. Key upregulated genes included NMNAT2 ( neuroprotection), PPM1H involved stress response), NRP1 , (axonal guidance formation synapses). showed reduced presence post-IS, enriched regulation pathways. exhibited proliferation displaying divergent developmental trajectories, suggesting altered differentiation pathways due stroke.Pseudotime revealed expression dynamics, early-stage (Cluster 1) showing greater stemness compared later-stage 2). Conclusion: provides detailed atlas after IS, highlighting critical astrocytes, repair. both related transmission neuronal These findings deepen our understanding recovery suggest potential therapeutic targets