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 H. Chang, Aruna Poduri, Brian Raftrey, Thanh Theresa Dinh, Walter A. Roper, Guang Li, Kelsey E. Quinn, Kathleen M. Caron, Sean Wu, Lucile Miquerol, Eugene C. Butcher, Irving Weissman, Stephen Quake and Kristy Red-Horse ()
Additional contact information
Tianying Su: Stanford University
Geoff Stanley: Stanford University
Rahul Sinha: Stanford University School of Medicine
Gaetano D’Amato: Stanford University
Soumya Das: Stanford University
Siyeon Rhee: Stanford University
Andrew H. Chang: Stanford University
Aruna Poduri: Stanford University
Brian Raftrey: Stanford University
Thanh Theresa Dinh: Veterans Affairs Palo Alto Health Care System and The Palo Alto Veterans Institute for Research
Walter A. Roper: Veterans Affairs Palo Alto Health Care System and The Palo Alto Veterans Institute for Research
Guang Li: Stanford University School of Medicine
Kelsey E. Quinn: University of North Carolina at Chapel Hill
Kathleen M. Caron: University of North Carolina at Chapel Hill
Sean Wu: Stanford University School of Medicine
Lucile Miquerol: Aix-Marseille Université
Eugene C. Butcher: Veterans Affairs Palo Alto Health Care System and The Palo Alto Veterans Institute for Research
Irving Weissman: Stanford University School of Medicine
Stephen Quake: Stanford University
Kristy Red-Horse: Stanford University

Nature, 2018, vol. 559, issue 7714, 356-362

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41586-018-0288-7

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