加拿大卡尔加里大学Jiami Guo团队近期取得重要工作进展，他们研究提出，星形胶质细胞的初级纤毛信号介导发育和区域特异性功能特化。相关研究成果2024年8月5日在线发表于《自然—神经科学》杂志上。

据介绍，星形胶质细胞多样性受局部环境调节的影响很大。

研究人员发现，小鼠大脑中的大多数星形胶质细胞都具有定位在细胞体上的单一初级纤毛。比较单细胞转录组学表明，初级纤毛介导典型的SHH信号传导，以调节星形胶质细胞亚型在突触调节、细胞内运输、能量和代谢中的特定核心特征。初级纤毛独立于典型的SHH信号传导，是星形胶质细胞形态和细胞内信号平衡的重要调节因子。

树突棘分析和转录组学表明，星形胶质细胞纤毛的紊乱会导致大脑中神经元发育和整体细胞间连接体的破坏。患有原发性纤毛缺陷星形胶质细胞的小鼠在感觉运动功能、社交能力、学习和记忆方面表现出行为缺陷。

总之，这一研究结果揭示了初级纤毛在传递局部信号方面的关键作用，这些信号驱动了发育中大脑星形胶质细胞的区域特异性多样化。

附：英文原文

Title: Primary cilia signaling in astrocytes mediates development and regional-specific functional specification

Author: Wang, Lizheng, Guo, Qianqian, Acharya, Sandesh, Zheng, Xiao, Huynh, Vanessa, Whitmore, Brandon, Yimit, Askar, Malhotra, Mehr, Chatterji, Siddharth, Rosin, Nicole, Labit, Elodie, Chipak, Colten, Gorzo, Kelsea, Haidey, Jordan, Elliott, David A., Ram, Tina, Zhang, Qingrun, Kuipers, Hedwich, Gordon, Grant, Biernaskie, Jeff, Guo, Jiami

Issue&Volume: 2024-08-05

Abstract: 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.

DOI: 10.1038/s41593-024-01726-z

Source: https://www.nature.com/articles/s41593-024-01726-z