CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Sci Adv. 2020 May 6;6(19):eaay9466. doi: 10.1126/sciadv.aay9466. eCollection 2020 May.
The cardiac and hematopoietic progenitors (CPs and HPs, respectively) in the mesoderm ultimately form a well-organized circulation system, but mechanisms that reconcile their development remain elusive. We found that activating transcription factor 3 () was highly expressed in the CPs, HPs, and mesoderm, in zebrafish. The mutants exhibited atrial dilated cardiomyopathy and a high ratio of immature myeloid cells. These manifestations were primarily caused by the blockade of differentiation of both CPs and HPs within the anterior lateral plate mesoderm. Mechanistically, Atf3 targets to repress -mediated glucose utilization. The high rate of glucose metabolism in mutants inhibited the differentiation of progenitors by changing the redox state. Therefore, could provide CPs and HPs with metabolic adaptive capacity to changes in glucose levels. Our study provides new insights into the role of in the coordination of differentiation of CPs and HPs by regulating glucose metabolism.
中胚层中的心脏和造血祖细胞（CP 和 HP）最终形成了一个组织良好的循环系统，但协调它们发育的机制仍不清楚。我们发现，在斑马鱼中，激活转录因子 3（）在 CP、HP 和中胚层中高度表达。突变体表现出心房扩张性心肌病和不成熟髓样细胞的高比例。这些表现主要是由于前侧板中胚层中 CP 和 HP 的分化受阻所致。在机制上，Atf3 靶向以抑制 - 介导的葡萄糖利用。在 突变体中，高葡萄糖代谢率通过改变氧化还原状态抑制祖细胞的分化。因此，可能为 CP 和 HP 提供代谢适应能力，以适应葡萄糖水平的变化。我们的研究为通过调节葡萄糖代谢来协调 CP 和 HP 的分化中 的作用提供了新的见解。
