Cell fate is established through coordinated gene expression programs in individual cells. Regulatory networks that include the Gata2 transcription factor play central roles in hematopoietic fate establishment. Although Gata2 is essential to the embryonic development and function of hematopoietic stem cells that form the adult hierarchy, little is known about the in vivo expression dynamics of Gata2 in single cells. Here, we examine Gata2 expression in single aortic cells as they establish hematopoietic fate in Gata2Venus mouse embryos. Time-lapse imaging reveals rapid pulsatile level changes in Gata2 reporter expression in cells undergoing endothelial-to-hematopoietic transition. Moreover, Gata2 reporter pulsatile expression is dramatically altered in Gata2^+/− aortic cells, which undergo fewer transitions and are reduced in hematopoietic potential. Our novel finding of dynamic pulsatile expression of Gata2 suggests a highly unstable genetic state in single cells concomitant with their transition to hematopoietic fate. This reinforces the notion that threshold levels of Gata2 influence fate establishment and has implications for transcription factor–related hematologic dysfunctions.

细胞命运是通过单个细胞中协调的基因表达程序建立的。包括Gata2转录因子在内的调控网络在造血命运的建立中起着核心作用。尽管Gata2对形成成年等级的造血干细胞的胚胎发育和功能至关重要，但对于Gata2在单个细胞中的体内表达动力学了解甚少。在这里，我们检查了Gata2在单个主动脉细胞中的表达，因为它们在Gata2Venus小鼠胚胎中建立了造血的命运。延时成像显示经历内皮细胞向造血细胞转化的细胞中Gata2报告基因表达的快速脉动水平变化。此外，Gata2报告子的脉动表达在Gata2 ^+/-中发生了显着变化主动脉细胞，其经历较少的转变并降低了造血潜能。我们对Gata2的动态搏动表达的新发现表明，单个细胞的高度不稳定的遗传状态与其向造血命运的过渡有关。这强化了以下观念：阈值水平的Gata2影响命运的建立，并与转录因子相关的血液功能障碍有关。