Nature Neurosci—小胶质细胞研究重磅突破：科学家开发MorphOMIC技术用于研究小胶质细胞的形态学表型

中文摘要

环境线索影响小胶质细胞的动态形态变化。表征这些变化的研究策略通常涉及用户选择的形态计量特征，这就排除了场景依赖的形态表型谱的识别。在这里，研究人员开发了MorphOMIC，一种拓扑数据分析方法，它能够将小胶质细胞形态半自动映射到线索相关表型图谱中，并克服特征选择偏差和生物变异性。他们提取了7个成年小鼠大脑区域的空间异质性和性别二分形态学表型。在两个神经变性小鼠模型中，这种性别特异性表型随着成熟而下降，但随着疾病的进展而增加，雌性小鼠在受影响的大脑区域表现出更快的形态学变化。值得注意的是，小胶质细胞的形态反映了重复暴露于氯胺酮麻醉后的适应，并且不能恢复到对照组的形态。最后，他们还证明长初级突起和短终末突起都为小胶质细胞形态学表型提供了独特的见解。总之，MorphOMICs为描述小胶质细胞形态开辟了一个新的视角。

英文摘要

Environmental cues influence the highly dynamic morphology of microglia. Strategies to characterize these changes usually involve user-selected morphometric features, which preclude the identification of a spectrum of context-dependent morphological phenotypes. Here we develop MorphOMICs, a topological data analysis approach, which enables semiautomatic mapping of microglial morphology into an atlas of cue-dependent phenotypes and overcomes feature-selection biases and biological variability. We extract spatially heterogeneous and sexually dimorphic morphological phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines with maturation but increases over the disease trajectories in two neurodegeneration mouse models, with females showing a faster morphological shift in affected brain regions. Remarkably, microglia morphologies reflect an adaptation upon repeated exposure to ketamine anesthesia and do not recover to control morphologies. Finally, we demonstrate that both long primary processes and short terminal processes provide distinct insights to morphological phenotypes. MorphOMICs opens a new perspective to characterize microglial morphology.

参考文献：A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes.Nat Neurosci. 2022 Oct;25(10):1379-1393.

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