Interferon gamma signaling positively regulates hematopoietic stem cell emergence.

ABSTRACT: Vertebrate hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region from "hemogenic" endothelium. Here we show that the proinflammatory cytokine interferon-? (IFN-?) and its receptor Crfb17 positively regulate HSC development in zebrafish. This regulation does not appear to modulate the proliferation or survival of HSCs or endothelial cells, but rather the endothelial-to-HSC transition. Notch signaling and blood flow positively regulate the expression of ifng and crfb17 in the AGM. Notably, IFN-? overexpression partially rescues the HSC loss observed in the absence of blood flow or Notch signaling. Importantly, IFN-? signaling acts cell autonomously to control the endothelial-to-HSC transition. IFN-? activates Stat3, an atypical transducer of IFN-? signaling, in the AGM, and Stat3 inhibition decreases HSC formation. Together, our findings uncover a developmental role for an inflammatory cytokine and place its action downstream of Notch signaling and blood flow to control Stat3 activation and HSC emergence.

SUBMITTER: Sawamiphak S 

PROVIDER: S-EPMC4371141 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature