A single-cell atlas of the normal and malformed human brain vasculature.
Ethan A WinklerChang N KimJayden M RossJoseph H GarciaEugene GilIrene OhLindsay Q ChenDavid WuJoshua S CatapanoKunal P RaygorKazim H NarsinhHelen KimShantel WeinsheimerDaniel L CookeBrian P WalcottMichael T LawtonNalin GuptaBerislav V ZlokovicEdward F ChangAdib A AblaDaniel A LimTomasz Jan NowakowskiPublished in: Science (New York, N.Y.) (2022)
Cerebrovascular diseases are a leading cause of death and neurologic disability. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of cerebrovascular cells in humans. We profiled transcriptomes of 181,388 cells to define a cell atlas of the adult human cerebrovasculature, including endothelial cell molecular signatures with arteriovenous segmentation and expanded perivascular cell diversity. By leveraging this reference, we investigated cellular and molecular perturbations in brain arteriovenous malformations, which are a leading cause of stroke in young people, and identified pathologic endothelial transformations with abnormal vascular patterning and the ontology of vascularly derived inflammation. We illustrate the interplay between vascular and immune cells that contributes to brain hemorrhage and catalog opportunities for targeting angiogenic and inflammatory programs in vascular malformations.
Keyphrases
- single cell
- rna seq
- endothelial cells
- induced apoptosis
- high throughput
- oxidative stress
- cell cycle arrest
- resting state
- endoplasmic reticulum stress
- healthcare
- atrial fibrillation
- cell therapy
- multiple sclerosis
- cerebral ischemia
- stem cells
- squamous cell carcinoma
- cell death
- deep learning
- functional connectivity
- machine learning
- genome wide
- neoadjuvant chemotherapy
- dna methylation
- convolutional neural network
- drug delivery
- vascular endothelial growth factor
- locally advanced
- high glucose
- subarachnoid hemorrhage
- pi k akt