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

Article

关键词: LAMINAR SHEAR-STRESS;    COUP-TFII;    RNA-SEQ;    SPROUTING ANGIOGENESIS;    ENDOTHELIAL-CELLS;    HEART;    CONTRIBUTES;    ENDOCARDIUM;    EXPRESSION;    PATHWAYS;   

DOI  :  10.1038/s41586-018-0288-7

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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