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Su, Tianying; Stanley, Geoff; Sinha, Rahul; D'Amato, Gaetano; Das, Soumya; Rhee, Siyeon; Chang, Andrew H; Poduri, Aruna; Raftrey, Brian; Dinh, Thanh Theresa; Roper, Walter A; Li, Guang; Quinn, Kelsey E; Caron, Kathleen M; Wu, Sean; Miquerol, Lucile; Butcher, Eugene C; Weissman, Irving; Quake, Stephen; Red-Horse, Kristy
Nature, 07/2018, Letnik: 559, Številka: 7714Journal Article
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.
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