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Updated: Nov 3, 2025
Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing
Published on: December 3, 2019
A map of transcriptional heterogeneity and regulatory variation in human microglia
Adam M H Young1,2,3, Natsuhiko Kumasaka2, Fiona Calvert2
1Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Abstract:
Microglia, the tissue-resident macrophages of the central nervous system (CNS), play critical roles in immune defense, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single-cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using a human induced pluripotent stem cell-based macrophage model to fine-map a candidate causal variant for Alzheimer's disease at the BIN1 locus. Our study provides a population-scale transcriptional map of a critically important cell for human CNS development and disease.
Insights
Researchers mapped human microglia gene expression, revealing how age, sex, and disease affect these crucial brain cells. This study provides a valuable resource for understanding central nervous system (CNS) development and neurodegenerative diseases.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia are essential immune cells in the central nervous system (CNS), vital for brain health and function.
- Obtaining sufficient human microglia for research is difficult, limiting our understanding of their role in disease.
- Existing knowledge of human microglia biology is constrained by limited sample sizes and accessibility.
Purpose of the Study:
- To create a comprehensive gene expression map of primary human microglia.
- To investigate the impact of demographic factors (age, sex) and clinical pathology on microglia.
- To identify genetic influences on microglia function using expression quantitative trait loci (eQTL) analysis.
Main Methods:
- Single-cell and bulk RNA sequencing of 141 primary human microglia samples.
- Expression quantitative trait loci (eQTL) mapping to link genetic variants to gene expression.
- Utilized human induced pluripotent stem cell-derived macrophages for variant fine-mapping.
Main Results:
- Detailed transcriptional profiles of human microglia across a large cohort.
- Identification of how age, sex, and neurological conditions alter microglia gene expression.
- Discovery of microglia-specific genetic variants influencing CNS function, including a candidate variant for Alzheimer's disease at the BIN1 locus.
Conclusions:
- This study establishes a population-scale transcriptional atlas of human microglia.
- Provides critical insights into the variability of microglia in health and disease.
- Offers a valuable resource for future research into CNS disorders and therapeutic targets.
