动脉
冠状动脉
祖细胞
静脉
生物
循环系统
干细胞
血流
细胞命运测定
细胞
内科学
医学
转录因子
细胞生物学
解剖
心脏病学
基因
遗传学
作者
Tianying Su,Geoff Stanley,Rahul Sinha,Gaetano D’Amato,Soumyashree Das,Siyeon Rhee,Andrew H. Chang,Aruna Poduri,Brian Raftrey,Thanh Theresa Dinh,Walter Roper,Guang Li,Kelsey E. Quinn,Kathleen M. Caron,Sean M. Wu,Lucile Miquerol,Eugene C. Butcher,Irving L. Weissman,Stephen R. Quake,Kristy Red‐Horse
出处
期刊:Nature
[Springer Nature]
日期:2018-07-01
卷期号:559 (7714): 356-362
被引量:211
标识
DOI:10.1038/s41586-018-0288-7
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. During development, new arteries can arise from pre-existing veins; the cell fate switch involved occurs gradually and before the onset of blood flow in mouse embryo hearts.
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