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Updated: Dec 2, 2025
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Induction and Micro-CT Imaging of Cerebral Cavernous Malformations in Mouse Model
Published on: September 4, 2017
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Mapping endothelial-cell diversity in cerebral cavernous malformations at single-cell resolution
Fabrizio Orsenigo1, Lei Liu Conze2, Suvi Jauhiainen2
1Vascular Biology Unit, FIRC Institute of Molecular Oncology Foundation (IFOM), Milan, Italy.
Elife
|November 3, 2020
Summary
Cerebral cavernous malformation (CCM) originates from specific venous endothelial cells, not arterial ones. This study reveals cellular origins of CCM lesions using advanced single-cell techniques.
Area of Science:
- Neuroscience
- Vascular Biology
- Genetics
Background:
- Cerebral cavernous malformation (CCM) is a rare neurovascular disorder.
- CCM is characterized by abnormal blood vessels leading to hemorrhage.
- Mutations in KRIT1, CCM2, or PDCD10 (CCM3) cause CCM.
Purpose of the Study:
- To comprehensively characterize brain endothelial cell (EC) subclasses in normal conditions and in a mouse model of CCM.
- To identify the specific EC subtypes involved in CCM lesion formation.
- To elucidate the molecular basis of CCM at the single-cell level.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq)
- Spatial transcriptomics
- Immunohistochemistry
- Mouse model of CCM with Pdcd10 deletion
Main Results:
- Arterial ECs are resistant to CCM transformation.
- A subset of angiogenic venous capillary ECs and endothelial progenitors are the origin of CCM lesions.
- scRNA-seq and spatial transcriptomics identified distinct EC subclasses involved in CCM.
Conclusions:
- CCM development involves specific venous endothelial cell populations.
- Understanding EC plasticity is key to CCM pathogenesis.
- This study provides novel single-cell insights into the molecular mechanisms of CCM disease.
