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

Elife. 2018 Sep 6;7:e36187. doi: 10.7554/eLife.36187.

Abstract

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.

Keywords: DNA methylation; Wnt; accessible chromatin; blood-brain barrier; chromosomes; gene expression; mouse; neuroscience; single cell RNA-seq; vascular endothelial cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Base Sequence
  • Brain / metabolism
  • Central Nervous System / cytology*
  • Chromatin / metabolism
  • DNA Methylation / genetics
  • Dopa Decarboxylase / metabolism
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism*
  • Epigenesis, Genetic*
  • Green Fluorescent Proteins / metabolism
  • Liver / metabolism
  • Lung / metabolism
  • Male
  • Mice, Transgenic
  • Multigene Family
  • Organ Specificity
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Wnt Signaling Pathway

Substances

  • Chromatin
  • RNA, Messenger
  • Transcription Factors
  • Green Fluorescent Proteins
  • Dopa Decarboxylase