Transcriptional and epigenomic landscapes of CNS and non-CNS vascular endothelial cells

• Published in: eLife 2018-09, Vol.7
• Main Authors: Sabbagh, Mark F, Heng, Jacob S, Luo, Chongyuan, Castanon, Rosa G, Nery, Joseph R, Rattner, Amir, Goff, Loyal A, Ecker, Joseph R, Nathans, Jeremy
• Format: Article
• Language: English
• Subjects: accessible chromatin; Amino Acid Motifs; Analysis; Animals; Arteries; Base Sequence; Biochemistry; Blood-brain barrier; Brain - metabolism; Central nervous system; Central Nervous System - cytology; Chromatin; Chromatin - metabolism; Chromosomes and Gene Expression; Deoxyribonucleic acid; DNA; DNA methylation; DNA Methylation - genetics; Dopa Decarboxylase - metabolism; Embryo; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Endothelium; Epigenesis, Genetic; Gene expression; Genes; Genetic aspects; Genetic research; Genomes; Genomics; Green Fluorescent Proteins - metabolism; Kidneys; Liver; Liver - metabolism; Lung - metabolism; Male; Medicine; Mice, Transgenic; Multigene Family; Neuroscience; Organ Specificity; Principal components analysis; Regulatory sequences; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Analysis, RNA; single cell RNA-seq; Single-Cell Analysis; Specialization; Tools and Resources; Transcription (Genetics); Transcription Factors - metabolism; Transcription, Genetic; vascular endothelial cell; Wnt; Wnt protein; Wnt Signaling Pathway
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.36187

Vascular endothelial cell (EC) function depends on appropriate organ-specific molecular and cellular specializations. To explore genomic mechanisms that control this specialization, we have analyzed and compared the transcriptome, accessible chromatin, and DNA methylome landscapes from mouse brain, liver, lung, and kidney ECs. Analysis of transcription factor (TF) gene expression and TF motifs at candidate -regulatory elements reveals both shared and organ-specific EC regulatory networks. In the embryo, only those ECs that are adjacent to or within the central nervous system (CNS) exhibit canonical Wnt signaling, which correlates precisely with blood-brain barrier (BBB) differentiation and expression. In the early postnatal brain, single-cell RNA-seq of purified ECs reveals (1) close relationships between veins and mitotic cells and between arteries and tip cells, (2) a division of capillary ECs into vein-like and artery-like classes, and (3) new endothelial subtype markers, including new validated tip cell markers.