MIC-MAC: An automated pipeline for high-throughput characterization and classification of three-dimensional microglia morphologies in mouse and human postmortem brain samples
MIC-MAC: An automated pipeline for high-throughput characterization and classification of three-dimensional microglia morphologies in mouse and human postmortem brain samples
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DOI：
10.1002/glia.23623
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发表时间：
2019-08-01
期刊：
影响因子：
6.2
通讯作者：
Skupin, Alexander
中科院分区：
文献类型：
--
作者：
Salamanca, Luis;Mechawar, Naguib;Skupin, Alexander
脑部疾病中小胶质细胞的表型变化特别多样化，它们在疾病进展中的作用（有益或有害）仍然难以捉摸。高通量分子方法如单细胞RNA测序现在可以解决特定生理条件下小胶质细胞群体的高度异质性，然而，不同小胶质细胞特征与其周围脑微环境之间的关系几乎不为人所知。因此，需要更好的工具来表征原位小胶质细胞的表型变异，特别是对于人脑死后样本的分析。为了应对这一挑战，我们开发了MIC-MAC，这是一种小胶质细胞和免疫细胞形态分析器和分类器管道，可以半自动分割，提取和分类小鼠和人脑样本的大型三维（3D）共聚焦图像堆栈中标记的所有小胶质细胞和免疫细胞。我们基于成像的方法能够对数千个小胶质细胞进行原位自动3D形态学表征和分类，并在小鼠衰老，人类阿尔茨海默病和Lewy Bodie样本痴呆中揭示了物种和疾病特异性形态表型。MIC-MAC是一种精确的诊断工具，可以对小鼠模型和患者大脑样本中的小胶质细胞形态状态进行快速，无偏见和大规模的分析。
The phenotypic changes of microglia in brain diseases are particularly diverse and their role in disease progression, beneficial, or detrimental, is still elusive. High-throughput molecular approaches such as single-cell RNA-sequencing can now resolve the high heterogeneity in microglia population for a specific physiological condition, however, the relation between the different microglial signatures and their surrounding brain microenvironment is barely understood. Thus, better tools to characterize the phenotypic variations of microglia in situ are needed, particularly for human brain postmortem samples analysis. To address this challenge, we developed MIC-MAC, a Microglia and Immune Cells Morphologies Analyser and Classifier pipeline that semiautomatically segments, extracts, and classifies all microglia and immune cells labeled in large three-dimensional (3D) confocal image stacks of mouse and human brain samples. Our imaging-based approach enables automatic 3D-morphology characterization and classification of thousands of individual microglia in situ and revealed species- and disease-specific morphological phenotypes in mouse aging, human Alzheimer's disease, and dementia with Lewy Bodie's samples. MIC-MAC is a precision diagnostic tool that allows a rapid, unbiased, and large-scale analysis of microglia morphological states in mouse models and patient brain samples.