Transcriptional and epigenomic landscapes of CNS and non-CNS vascular endothelial cells.
Mark F SabbaghJacob S HengChongyuan LuoRosa G CastanonJoseph R NeryAmir RattnerChristopher A WalshJoseph R EckerJeremy NathansPublished in: eLife (2018)
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 cis-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 Zic3 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.
Keyphrases
- blood brain barrier
- single cell
- rna seq
- transcription factor
- endothelial cells
- gene expression
- induced apoptosis
- cerebral ischemia
- cell cycle arrest
- high throughput
- genome wide
- dna binding
- dna methylation
- endoplasmic reticulum stress
- oxidative stress
- poor prognosis
- cell death
- single molecule
- cell free
- vascular endothelial growth factor
- high glucose
- signaling pathway
- circulating tumor
- stem cells
- pregnant women
- cell cycle
- multiple sclerosis
- nucleic acid
- mesenchymal stem cells