Ensembles of endothelial and mural cells promote angiogenesis in prenatal human brain.
Cell
; 185(20): 3753-3769.e18, 2022 09 29.
Article
em En
| MEDLINE
| ID: mdl-36179668
ABSTRACT
Interactions between angiogenesis and neurogenesis regulate embryonic brain development. However, a comprehensive understanding of the stages of vascular cell maturation is lacking, especially in the prenatal human brain. Using fluorescence-activated cell sorting, single-cell transcriptomics, and histological and ultrastructural analyses, we show that an ensemble of endothelial and mural cell subtypes tile the brain vasculature during the second trimester. These vascular cells follow distinct developmental trajectories and utilize diverse signaling mechanisms, including collagen, laminin, and midkine, to facilitate cell-cell communication and maturation. Interestingly, our results reveal that tip cells, a subtype of endothelial cells, are highly enriched near the ventricular zone, the site of active neurogenesis. Consistent with these observations, prenatal vascular cells transplanted into cortical organoids exhibit restricted lineage potential that favors tip cells, promotes neurogenesis, and reduces cellular stress. Together, our results uncover important mechanisms into vascular maturation during this critical period of human brain development.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neovascularização Fisiológica
/
Células Endoteliais
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article