Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form. This physical transformation of neurons is facilitated by the engulfment and degradation of axonal branches and synapses by surrounding glial cells, including microglia and astrocytes. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia have made it difficult to define the contribution of these and other glial cell types to this crucial process. Here, we used large-scale, serial section transmission electron microscopy (TEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex, providing unprecedented resolution of their morphology and composition. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors, frequently surrounded small branches of axons. Numerous phagosomes and phagolysosomes (PLs) containing fragments of axons and vesicular structures were present inside their processes, suggesting that OPCs engage in axon pruning. Single-nucleus RNA sequencing from the developing mouse cortex revealed that OPCs express key phagocytic genes at this stage, as well as neuronal transcripts, consistent with active axon engulfment. Although microglia are thought to be responsible for the majority of synaptic pruning and structural refinement, PLs were ten times more abundant in OPCs than in microglia at this stage, and these structures were markedly less abundant in newly generated oligodendrocytes, suggesting that OPCs contribute substantially to the refinement of neuronal circuits during cortical development.

中文翻译：

---

少突胶质细胞前体细胞摄取小鼠新皮质中的轴突

随着新生电路采用其成熟形式，发育中的大脑中的神经元经历了广泛的结构改进。周围神经胶质细胞（包括小胶质细胞和星形胶质细胞）对轴突分支和突触的吞噬和降解促进了神经元的这种物理转化。然而，吞噬细胞器的小尺寸和复杂、高度分支的神经胶质形态使得很难定义这些和其他神经胶质细胞类型对这一关键过程的贡献。在这里，我们使用具有计算体积分割的大规模连续切片透射电子显微镜 (TEM) 来重建小鼠视觉皮层中不同神经胶质类型的完整 3D 形态，提供其形态和组成的前所未有的分辨率。不料，我们发现少突胶质细胞前体细胞 (OPC) 的精细过程，即大量、高度动态的神经胶质祖细胞，经常包围轴突的小分支。许多包含轴突片段和囊泡结构的吞噬体和吞噬溶酶体 (PL) 存在于它们的过程中，表明 OPC 参与轴突修剪。来自发育中的小鼠皮层的单核 RNA 测序表明，OPC 在此阶段表达关键的吞噬基因以及神经元转录本，这与活跃的轴突吞噬一致。尽管小胶质细胞被认为是大部分突触修剪和结构细化的原因，但在此阶段，OPC 中的 PL 含量是小胶质细胞中的十倍，而这些结构在新生成的少突胶质细胞中的含量明显较低，