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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.

Rescue of hematopoietic stem/progenitor cells formation in plcg1 zebrafish mutant