Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou, P.R. China.
Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, P.R. China.
J Biol Chem. 2021 Jan-Jun;296:100272. doi: 10.1016/j.jbc.2021.100272. Epub 2021 Jan 9.
Neutrophils play an essential role in the innate immune defense system in vertebrates. During hematopoiesis, the full function of neutrophils involves maturation of granules and related enzymes. Yet, transcription regulators that promote neutrophil maturation remain largely undefined. Here, two hematopoiesis-defective zebrafish mutants, runx1 and c-myb, were used to investigate the in vivo roles of Runx1 in cooperation with c-Myb in regulating neutrophil maturation. Loss of runx1 impairs primitive neutrophil development. Additional regulation of c-myb and c-myb induces a more severe phenotypes suggesting a synergistic genetic interaction between c-myb and runx1 in neutrophil maturation. Further studies revealed that the two transcription factors act cooperatively to control neutrophil maturation processes via transactivating a series of neutrophil maturation-related genes. These data reveal the in vivo roles of Runx1 in regulating primitive neutrophil maturation while also indicating a novel genetic and molecular orchestration of Runx1 and c-Myb in myeloid cell development. The study will provide new evidence on the regulation of neutrophil maturation during hematopoiesis.
中性粒细胞在脊椎动物的先天免疫防御系统中发挥着重要作用。在造血过程中，中性粒细胞的全部功能涉及颗粒和相关酶的成熟。然而，促进中性粒细胞成熟的转录调节因子在很大程度上仍未得到定义。在这里，使用两种造血缺陷的斑马鱼突变体，runx1 和 c-myb，来研究 Runx1 在与 c-Myb 合作调节中性粒细胞成熟中的体内作用。Runx1 的缺失会损害原始中性粒细胞的发育。c-myb 的额外调节和 c-myb 的诱导导致更严重的表型，表明 c-myb 和 runx1 在中性粒细胞成熟中存在协同的遗传相互作用。进一步的研究表明，这两个转录因子通过反式激活一系列与中性粒细胞成熟相关的基因，协同作用来控制中性粒细胞成熟过程。这些数据揭示了 Runx1 在调节原始中性粒细胞成熟中的体内作用，同时也表明了 Runx1 和 c-Myb 在髓样细胞发育中的新型遗传和分子协调作用。该研究将为造血过程中中性粒细胞成熟的调控提供新的证据。
