Microglial phagocytosis of single dying oligodendrocytes is mediated by CX3CR1 but not MERTK.
Microglial phagocytosis of single dying oligodendrocytes is mediated by CX3CR1 but not MERTK.
复制标题
小胶质细胞对单个死亡少突胶质细胞的吞噬作用是由 CX3CR1 介导的，而不是 MERTK。
DOI：
10.1101/2023.12.11.570620
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Hill,RobertA
中科院分区：
文献类型：
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作者：
Olveda,GenaroE;Barasa,MaryanneN;Hill,RobertA
少突胶质细胞死亡在衰老和神经退行性疾病中很常见。在这些条件下，必须有效去除垂死的少突胶质细胞，以实现髓鞘再生并防止前馈退行性级联反应。这种细胞碎片的去除被认为主要是由常驻小胶质细胞进行的。为了研究小胶质细胞是如何做到这一点的细胞动力学，我们使用了单细胞皮质脱髓鞘模型结合纵向活体成像的双标记转基因小鼠。在吞噬作用之后，单个小胶质细胞通过精确、快速和定型的序列在一天内清除靶向少突胶质细胞及其髓鞘。Fractalkine受体CX3CR 1的缺失延迟了小胶质细胞对细胞索马体的吞噬作用，但对髓鞘的清除没有影响。出乎意料的是，磷脂酰丝氨酸受体MERTK的缺失对少突胶质细胞或髓鞘清除没有影响。因此，使用单独的分子信号来检测、接合和清除垂死少突胶质细胞的不同亚区室，以维持组织稳态。
Oligodendrocyte death is common in aging and neurodegenerative disease. In these conditions, dying oligodendrocytes must be efficiently removed to allow remyelination and to prevent a feedforward degenerative cascade. Removal of this cellular debris is thought to primarily be carried out by resident microglia. To investigate the cellular dynamics underlying how microglia do this, we use a single-cell cortical demyelination model combined with longitudinal intravital imaging of dual-labeled transgenic mice. Following phagocytosis, single microglia clear the targeted oligodendrocyte and its myelin sheaths in one day via a precise, rapid, and stereotyped sequence. Deletion of the fractalkine receptor, CX3CR1, delays the microglial phagocytosis of the cell soma but has no effect on clearance of myelin sheaths. Unexpectedly, deletion of the phosphatidylserine receptor, MERTK, has no effect on oligodendrocyte or myelin sheath clearance. Thus, separate molecular signals are used to detect, engage, and clear distinct sub-compartments of dying oligodendrocytes to maintain tissue homeostasis.