1. Ensembles of endothelial and mural cells promote angiogenesis in prenatal human brain
- Author
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Crouch, Elizabeth E, Bhaduri, Aparna, Andrews, Madeline G, Cebrian-Silla, Arantxa, Diafos, Loukas N, Birrueta, Janeth Ochoa, Wedderburn-Pugh, Kaylee, Valenzuela, Edward J, Bennett, Neal K, Eze, Ugomma C, Sandoval-Espinosa, Carmen, Chen, Jiapei, Mora, Cristina, Ross, Jayden M, Howard, Clare E, Gonzalez-Granero, Susana, Lozano, Jaime Ferrer, Vento, Maximo, Haeussler, Maximilian, Paredes, Mercedes F, Nakamura, Ken, Garcia-Verdugo, Jose Manuel, Alvarez-Buylla, Arturo, Kriegstein, Arnold R, and Huang, Eric J
- Subjects
Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,Neurosciences ,Stem Cell Research ,Pediatric ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Brain ,Collagen ,Endothelial Cells ,Humans ,Laminin ,Midkine ,Neovascularization ,Pathologic ,Neovascularization ,Physiologic ,Pericytes ,angiogenesis ,arterial endothelial cells ,blood brain barrier ,cortical organoids ,endothelial cells ,human prenatal brain development ,mural cells ,pericytes ,smooth muscle cells ,tip cells ,venous and capillary endothelial cells ,ventricular zone ,Human prenatal brain development ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - 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.
- Published
- 2022