Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Nat Neurosci. 2024 Sep;27(9):1708-1720. doi: 10.1038/s41593-024-01726-z. Epub 2024 Aug 5.
Astrocyte diversity is greatly influenced by local environmental modulation. Here we report that the majority of astrocytes across the mouse brain possess a singular primary cilium localized to the cell soma. Comparative single-cell transcriptomics reveals that primary cilia mediate canonical SHH signaling to modulate astrocyte subtype-specific core features in synaptic regulation, intracellular transport, energy and metabolism. Independent of canonical SHH signaling, primary cilia are important regulators of astrocyte morphology and intracellular signaling balance. Dendritic spine analysis and transcriptomics reveal that perturbation of astrocytic cilia leads to disruption of neuronal development and global intercellular connectomes in the brain. Mice with primary ciliary-deficient astrocytes show behavioral deficits in sensorimotor function, sociability, learning and memory. Our results uncover a critical role for primary cilia in transmitting local cues that drive the region-specific diversification of astrocytes within the developing brain.
星形胶质细胞的多样性受局部环境调节的极大影响。在这里，我们报告说，在整个小鼠大脑中，大多数星形胶质细胞都拥有一个位于细胞体的独特初级纤毛。比较单细胞转录组学揭示，初级纤毛介导经典 SHH 信号转导，以调节突触调节、细胞内运输、能量和代谢中星形胶质细胞亚型特异性的核心特征。独立于经典 SHH 信号，初级纤毛是星形胶质细胞形态和细胞内信号平衡的重要调节剂。树突棘分析和转录组学揭示，星形胶质细胞纤毛的扰动导致大脑中神经元发育和全局细胞间连接体的破坏。初级纤毛缺陷型星形胶质细胞的小鼠在感觉运动功能、社交性、学习和记忆方面表现出行为缺陷。我们的结果揭示了初级纤毛在传递局部信号中的关键作用，这些信号驱动了发育中的大脑中星形胶质细胞的区域特异性多样化。
