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

Tianying Su , Geoff Stanley , Rahul Sinha , Gaetano d'Amato , Soumya Das , Siyeon Rhee , Andrew Chang , Aruna Poduri , Brian Raftrey , Thanh Theresa Dinh , Walter Roper , Guang Li (1) , Kelsey Quinn , Kathleen Caron , Sean Wu , Lucile Miquerol (2) , Eugene Butcher , Irving Weissman , Stephen Quake , Kristy Red-Horse

1 Department of Control Science and Engineering
2 IBDM - Institut de Biologie du Développement de Marseille

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.

Domaines: Sciences du Vivant [q-bio]

Tianying Su, Geoff Stanley, Rahul Sinha, Gaetano d'Amato, Soumya Das, et al.. Single-cell analysis of early progenitor cells that build coronary arteries. Nature, 2018, 559 (7714), pp.356-362. ⟨10.1038/s41586-018-0288-7⟩. ⟨hal-01993721⟩