Abstract TP225: Cell-type-based Pathway Analysis In Experimental Subarachnoid Hemorrhage
Stroke(2023)
摘要
Introduction: Recently, increasing evidence points to a pivotal role of neuroinflammation in the pathogenesis of Subarachnoid hemorrhage (SAH). However, the pattern of cell interaction after SAH is not clear. Methods: Endovascular perforation (EVP) murine SAH model was established to reproduce experimental SAH. Post-SAH CD11b+ single-cell suspension was harvested at day 3 and sequenced using 10X single-cell RNA-sequencing platform. Then, the detailed single-cell information of post-SAH cells was analyzed with bioinformatics. The same pathways and related ligand-receptors in microglia and other cells were compared. Results: More than 51 pathways were found in the crosstalk of brain cells after SAH, these cells including: microglia (microglia worked in 25 pathways), CNS-associated macrophage, astrocyte, neuron, monocyte and macrophage and Oligodendrocyte. In the microglia subsets’ interaction, 15 pathways upregulated, of which four pathways were specific to microglia subsets, including amyloid-β precursor protein (APP), Tumor necrosis factor (TNF), growth differentiation factor (GDF) and oncostatin M (OSM) signaling pathways. We precisely distinguished the ligand-receptor pattern in which microglia differ with other cells in 7 pathways, including chemokine ligands (CCL), colony-stimulating factor (CSF), GALECTIN, growth arrest-specific (GAS), intercellular adhesion molecule (ICAM), junction adhesion molecule (JAM) and secreted phosphoprotein 1 (SPP1) signaling pathways. Gene ontology (GO) results showed that compared with non-microglia cells, post-SAH microglia with upregulated function like leukocyte, glia cell activation and migration, while have downregulated functions of protein-lipid complex remodeling. Conclusions: Collectively, we first systematically report the interaction patterns of seven brain cells after SAH. Further the cell type based ligand-receptor analysis of microglia and other cells in the same pathway was comparatively conducted. These results revealed the cellular mechanisms for neuroinflammation after SAH, and the ligand-receptor results provided a theoretical basis and opportunities for accurate monitoring and modulation of SAH in the future.
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abstract tp225,pathway analysis,cell-type-based
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