Applied Immunology Laboratory, Department of Thoracic Surgery, Medical University of Vienna, 1090, Vienna, Austria.
Aposcience AG, 1200, Vienna, Austria.
Nat Commun. 2024 Jul 24;15(1):6232. doi: 10.1038/s41467-024-50465-z.
Neuroglia critically shape the brain´s response to ischemic stroke. However, their phenotypic heterogeneity impedes a holistic understanding of the cellular composition of the early ischemic lesion. Here we present a single cell resolution transcriptomics dataset of the brain´s acute response to infarction. Oligodendrocyte lineage cells and astrocytes range among the most transcriptionally perturbed populations and exhibit infarction- and subtype-specific molecular signatures. Specifically, we find infarction restricted proliferating oligodendrocyte precursor cells (OPCs), mature oligodendrocytes and reactive astrocytes, exhibiting transcriptional commonalities in response to ischemic injury. OPCs and reactive astrocytes are involved in a shared immuno-glial cross talk with stroke-specific myeloid cells. Within the perilesional zone, osteopontin positive myeloid cells accumulate in close proximity to CD44 proliferating OPCs and reactive astrocytes. In vitro, osteopontin increases the migratory capacity of OPCs. Collectively, our study highlights molecular cross talk events which might govern the cellular composition of acutely infarcted brain tissue.
神经胶质细胞对大脑对缺血性中风的反应起着至关重要的作用。然而，它们表型的异质性阻碍了对早期缺血性病变细胞组成的全面理解。在这里，我们呈现了一个大脑对梗死急性反应的单细胞分辨率转录组数据集。少突胶质细胞谱系细胞和星形胶质细胞是转录变化最明显的群体之一，表现出与梗死和亚型特异性的分子特征。具体来说，我们发现局限于梗死的增殖少突胶质细胞前体细胞（OPC）、成熟少突胶质细胞和反应性星形胶质细胞，在对缺血性损伤的反应中表现出转录上的共性。OPC 和反应性星形胶质细胞参与与中风特异性髓样细胞的共同免疫-神经胶质相互作用。在病灶周围区域，骨桥蛋白阳性的髓样细胞与 CD44 增殖的 OPC 和反应性星形胶质细胞紧密相邻聚集。在体外，骨桥蛋白增加了 OPC 的迁移能力。总的来说，我们的研究强调了可能支配急性梗死脑组织细胞组成的分子交叉对话事件。
