Single-cell sequencing insights into the transcriptional landscape of cerebral cavernous malformations

Abstract

Cerebral cavernous malformations (CCMs) are deemed to be acquired vascular anomalies that serve as a frequent driving force of a series of symptoms in central nervous system including hemorrhage, seizures and focal neurologic deficits, with an unknown etiology and no specific medication. For a long time, CCMs-associated studies mainly focus on investigating genetic mutations as well as vasculature-associated phenotypes. Notably, an increasing number of studies have recently revealed that inflammation and the heterogeneity of endothelial cells (ECs) play crucial roles in influencing the development of cavernomas, which ultimately exerts striking impacts on CCMs disease progression and patient outcomes. Interestingly, emerging single-cell RNA sequencing (scRNA-seq) technology has been validated to be essential for uncovering the molecular basis of multiple cell types involved in governing the development of CCMs disease. Herein, we comprehensively review recent advances in the applications of scRNA-seq technology in various CCMs models. Moreover, we concentrate on ECs, mural cells, fibroblasts, astrocytes as well as immune cells, predominantly exploring their unique transcriptional landscapes and contribution to the CCM pathologic progression. Finally, we summarize the therapies targeting these distinct cell populations in CCMs disease, aiming at identifying promising therapeutic strategies for retarding the development of CCMs.