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

Abstract

SUMMARYArteries 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 cell fate conversion. Using scRNA-Seq and mouse genetics, we discovered 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. Prior to coronary blood flow, pre-artery cells appeared within the immature vessel plexus, expressed mature artery markers, and decreased cell cycling. The vein specifying transcription factor, Coup-tf2, blocked plexus cells from overcoming the pre-artery threshold through inducing cell cycle genes. Thus, vein-derived coronary arteries are built by pre-artery cells that can differentiate independent of blood flow upon the release of COUP-TF2/cell cycle factor-mediated inhibition.