Single-cell analysis of early progenitor cells that build coronary arteries

Nature. 2018 Jul;559(7714):356-362. doi: 10.1038/s41586-018-0288-7. Epub 2018 Jul 4.

Abstract

Arteries and veins are specified by antagonistic transcriptional programs. However, during development and regeneration, new arteries can arise from pre-existing veins through a poorly understood process of cell fate conversion. Here, using single-cell RNA sequencing and mouse genetics, we show that vein cells of the developing heart undergo an early cell fate switch to create a pre-artery population that subsequently builds coronary arteries. Vein cells underwent a gradual and simultaneous switch from venous to arterial fate before a subset of cells crossed a transcriptional threshold into the pre-artery state. Before the onset of coronary blood flow, pre-artery cells appeared in the immature vessel plexus, expressed mature artery markers, and decreased cell cycling. The vein-specifying transcription factor COUP-TF2 (also known as NR2F2) prevented plexus cells from overcoming the pre-artery threshold by inducing cell cycle genes. Thus, vein-derived coronary arteries are built by pre-artery cells that can differentiate independently of blood flow upon the release of inhibition mediated by COUP-TF2 and cell cycle factors.

Publication types

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

MeSH terms

  • Animals
  • Arteries / cytology*
  • Arteries / metabolism
  • COUP Transcription Factor II / metabolism
  • Cell Cycle / genetics
  • Cell Differentiation
  • Cell Lineage
  • Coronary Vessels / cytology*
  • Coronary Vessels / metabolism
  • Female
  • Male
  • Mice
  • Sequence Analysis, RNA
  • Single-Cell Analysis*
  • Stem Cells / cytology*
  • Stem Cells / metabolism*
  • Veins / cytology*
  • Veins / metabolism

Substances

  • COUP Transcription Factor II
  • Nr2f2 protein, mouse