First Author | Su T | Year | 2018 |
Journal | Nature | Volume | 559 |
Issue | 7714 | Pages | 356-362 |
PubMed ID | 29973725 | Mgi Jnum | J:351812 |
Mgi Id | MGI:7703842 | Doi | 10.1038/s41586-018-0288-7 |
Citation | Su T, et al. (2018) Single-cell analysis of early progenitor cells that build coronary arteries. Nature 559(7714):356-362 |
abstractText | 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. |