Nature Communications ( IF 14.7 ) Pub Date : 2024-07-24 , DOI: 10.1038/s41467-024-50465-z Daniel Bormann 1, 2 , Michael Knoflach 3, 4 , Emilia Poreba 5 , Christian J Riedl 6, 7 , Giulia Testa 6, 7 , Cyrille Orset 8, 9 , Anthony Levilly 8, 9 , Andréa Cottereau 8, 9 , Philipp Jauk 6, 7, 10 , Simon Hametner 6, 7 , Nadine Stranzl 6, 7 , Bahar Golabi 5 , Dragan Copic 1, 2, 11 , Katharina Klas 1, 2 , Martin Direder 1, 2, 12 , Hannes Kühtreiber 1, 2 , Melanie Salek 1, 2 , Stephanie Zur Nedden 13 , Gabriele Baier-Bitterlich 13 , Stefan Kiechl 3, 4 , Carmen Haider 6, 7 , Verena Endmayr 6, 7 , Romana Höftberger 6, 7 , Hendrik J Ankersmit 1, 2 , Michael Mildner 5
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.
中文翻译:
单核 RNA 测序揭示了雄性啮齿动物神经胶质细胞类型对缺血性中风的特异性反应
神经胶质细胞对大脑对缺血性中风的反应至关重要。然而,它们的表型异质性阻碍了对早期缺血性病变的细胞组成的整体理解。在这里,我们提出了大脑对梗塞的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属于转录扰动最严重的群体,并表现出梗塞和亚型特异性分子特征。具体来说,我们发现梗死限制增殖的少突胶质细胞前体细胞(OPC)、成熟的少突胶质细胞和反应性星形胶质细胞,在响应缺血性损伤时表现出转录共性。 OPC 和反应性星形胶质细胞参与与中风特异性骨髓细胞的共同免疫神经胶质细胞对话。在病灶周围区域,骨桥蛋白阳性骨髓细胞聚集在 CD44 +增殖的 OPC 和反应性星形胶质细胞附近。在体外,骨桥蛋白增加 OPC 的迁移能力。总的来说,我们的研究强调了可能控制急性梗塞脑组织细胞组成的分子串扰事件。