Mapping endothelial-cell diversity in cerebral cavernous malformations at single-cell resolution

eLife

Peetra Ulrica Magnusson¹  Lei Liu Conze²  Maria Ascención Globisch²  Suvi Jauhiainen²  Sara Isabel Cunha²  Johan Brännström²  Veronica Sundell²  Elisabetta Dejana²  Fabrizio Orsenigo³  Matteo Malinverno³  Claudio Maderna³  Monica Corada³  Francesca Lazzaroni³  Maria Grazia Lampugnani³ 

[1] Mario Negri Institute for Pharmacological Research, Milan, Italy;Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;Vascular Biology Unit, FIRC Institute of Molecular Oncology Foundation (IFOM), Milan, Italy;

关键词: vascular biology;    blood brain barrier;    cerebral cavernous malformation;    spatial transcriptomics;    vascular disease;    single cell RNA sequencing;   

DOI  :  10.7554/eLife.61413

来源: DOAJ

【 摘 要 】

Cerebral cavernous malformation (CCM) is a rare neurovascular disease that is characterized by enlarged and irregular blood vessels that often lead to cerebral hemorrhage. Loss-of-function mutations to any of three genes results in CCM lesion formation; namely, KRIT1, CCM2, and PDCD10 (CCM3). Here, we report for the first time in-depth single-cell RNA sequencing, combined with spatial transcriptomics and immunohistochemistry, to comprehensively characterize subclasses of brain endothelial cells (ECs) under both normal conditions and after deletion of Pdcd10 (Ccm3) in a mouse model of CCM. Integrated single-cell analysis identifies arterial ECs as refractory to CCM transformation. Conversely, a subset of angiogenic venous capillary ECs and respective resident endothelial progenitors appear to be at the origin of CCM lesions. These data are relevant for the understanding of the plasticity of the brain vascular system and provide novel insights into the molecular basis of CCM disease at the single cell level.

【 授权许可】

Unknown