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Updated: Jan 26, 2026

Derivation of a Human Brain Organoid with Microglia Development
Published on: January 17, 2025
MIC-MAC: An automated pipeline for high-throughput characterization and classification of three-dimensional microglia
Luis Salamanca1,2, Naguib Mechawar3, Keith K Murai4
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg.
Abstract:
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.
Insights
Researchers developed MIC-MAC, a tool to analyze microglia morphology in brain diseases. This imaging pipeline reveals distinct microglial phenotypes in mouse and human samples, aiding disease research.
Area of Science:
- Neuroscience
- Immunology
- Computational Biology
Background:
- Microglia exhibit diverse phenotypic changes in brain diseases, with their exact role remaining unclear.
- Understanding microglial heterogeneity and their interaction with the brain microenvironment is crucial but challenging.
- Existing methods struggle to analyze microglial phenotypes in situ, especially in human postmortem samples.
Purpose of the Study:
- To develop an advanced tool for characterizing microglial phenotypic variations in situ.
- To enable detailed morphological analysis of microglia in both mouse and human brain samples.
- To facilitate unbiased, large-scale assessment of microglial states in neurological conditions.
Main Methods:
- Development of MIC-MAC (Microglia and Immune Cells Morphologies Analyser and Classifier) pipeline.
- Semiautomatic segmentation, extraction, and classification of microglia and immune cells from 3D confocal image stacks.
- Application of the imaging-based approach to analyze mouse aging and human Alzheimer's disease and dementia with Lewy bodies samples.
Main Results:
- MIC-MAC successfully performed 3D morphological characterization and classification of thousands of individual microglia in situ.
- The pipeline identified species- and disease-specific microglial morphological phenotypes.
- Demonstrated the tool's capability in analyzing complex neurological disease models and patient tissues.
Conclusions:
- MIC-MAC provides a powerful, imaging-based method for analyzing microglial morphology in situ.
- The tool enables rapid, unbiased, and large-scale characterization of microglial states.
- MIC-MAC serves as a precision diagnostic aid for studying microglia in brain diseases across species.
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