The Biomedical/Biotechnology Research Institute, North Carolina Central University, North Carolina Research Campus, Nutrition Research Building, Kannapolis, NC, 28081, USA.
Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina A&T State University, North Carolina Research Campus, Nutrition Research Building, Kannapolis, NC, 28081, USA.
Sci Rep. 2019 Jan 21;9(1):244. doi: 10.1038/s41598-018-36338-8.
Hematopoietic stem/progenitor cells (HSPC) in zebrafish emerge from the aortic hemogenic endothelium (HE) and migrate towards the caudal hematopoietic tissue (CHT), where they expand and differentiate during definitive hematopoiesis. Phospholipase C gamma 1 (Plcγ1) has been implicated for hematopoiesis in vivo and in vitro and is also required to drive arterial and HSPC formation. Genetic mutation in plcg1 (y10 allele) completely disrupts the aortic blood flow, specification of arterial fate, and HSPC formation in zebrafish embryos. We previously demonstrated that ginger treatment promoted definitive hematopoiesis via Bmp signaling. In this paper, we focus on HSPC development in plcg1 mutants and show that ginger/10-gingerol (10-G) can rescue the expression of arterial and HSPC markers in the HE and CHT in plcg1 mutant embryos. We demonstrate that ginger can induce scl/runx1 expression, and that rescued HE fate is dependent on Bmp and Notch. Bmp and Notch are known to regulate nitric oxide (NO) production and NO can induce hematopoietic stem cell fate. We show that ginger produces a robust up-regulation of NO. Taken together, we suggest in this paper that Bmp, Notch and NO are potential players that mediate the effect of ginger/10-G for rescuing the genetic defects in blood vessel specification and HSPC formation in plcg1 mutants. Understanding the molecular mechanisms of HSPC development in vivo is critical for understanding HSPC expansion, which will have a positive impact in regenerative medicine.
斑马鱼的造血干/祖细胞 (HSPC) 来源于主动脉造血内皮 (HE)，并迁移到尾造血组织 (CHT)，在那里它们在确定性造血过程中扩增和分化。磷脂酶 C 伽马 1 (Plcγ1) 已被证明在体内和体外参与造血，并需要驱动动脉和 HSPC 的形成。 plcg1 (y10 等位基因) 的基因突变完全破坏了主动脉血流、动脉命运的指定和斑马鱼胚胎中 HSPC 的形成。我们之前证明，生姜处理通过 Bmp 信号促进确定性造血。在本文中，我们专注于 plcg1 突变体中的 HSPC 发育，并表明生姜/10-姜酚 (10-G) 可以挽救 plcg1 突变体胚胎中 HE 和 CHT 中动脉和 HSPC 标记物的表达。我们证明生姜可以诱导 scl/runx1 的表达，并且挽救的 HE 命运依赖于 Bmp 和 Notch。众所周知，Bmp 和 Notch 调节一氧化氮 (NO) 的产生，而 NO 可以诱导造血干细胞命运。我们表明生姜会产生强烈的 NO 上调。综上所述，我们在本文中提出，Bmp、Notch 和 NO 是介导生姜/10-G 拯救 plcg1 突变体中血管指定和 HSPC 形成的遗传缺陷的潜在作用因子。了解体内 HSPC 发育的分子机制对于理解 HSPC 的扩增至关重要，这将对再生医学产生积极影响。
