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Updated: Aug 5, 2026
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Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing
Published on: December 3, 2019
Single-Cell RNA Sequencing Characterizes Microglial Phenotypic Heterogeneity Across Different Stroke Subtypes
Yiyan Guo1, Tongtong Xu1, Chang Liu1,2
1Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Department of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Aging and Disease
|July 27, 2026
Summary
Microglia activation differs across stroke types, with acute strokes showing rapid responses and chronic hypoperfusion delayed responses. Shared chronic activation patterns emerge later, offering targets for tailored immunotherapies.
Area of Science:
- Neuroscience
- Immunology
- Genomics
Background:
- Microglia-driven neuroinflammation is crucial in secondary brain injury.
- Understanding microglial temporal and subtype-specific responses in cerebrovascular diseases is limited.
Purpose of the Study:
- To profile the temporal transcriptomic landscape of microglia in response to different stroke subtypes.
- To elucidate divergent and convergent microglial activation patterns.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was used on mouse models of ischemic stroke (IS), hemorrhagic stroke (HS), and chronic cerebral hypoperfusion (CCH).
- Samples were collected at 3, 7, and 14 days post-injury.
Main Results:
- A temporal mismatch in microglial activation was observed: IS and HS showed early (3-day) activation, while CCH exhibited a delayed (14-day) transition.
- HS revealed a unique S100A8+/CHIL3+ inflammatory cluster in the hyperacute phase.
- All models displayed a shared chronic activation pattern by day 14, with SPP1+ DAM-like and MHC-II signatures.
- A pre-existing stress signature (Hspa1a+/Hspa1b+) was identified in white matter microglia.
Conclusions:
- Distinct temporal microglial responses occur across different stroke etiologies.
- Shared chronic microglial signatures suggest common pathways in later stroke stages.
- These findings provide a framework for developing stage-specific immunotherapies for cerebrovascular diseases.
