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Interferon gamma signaling positively regulates hematopoietic stem cell emergence

Item Type:Article
Title:Interferon gamma signaling positively regulates hematopoietic stem cell emergence
Creators Name:Sawamiphak, S. and Kontarakis, Z. and Stainier, D.Y.R.
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-{gamma} (IFN-{gamma}) 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-{gamma} overexpression partially rescues the HSC loss observed in the absence of blood flow or Notch signaling. Importantly, IFN-{gamma} signaling acts cell autonomously to control the endothelial-to-HSC transition. IFN-{gamma}activates Stat3, an atypical transducer of IFN-{gamma}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.
Keywords:Aorta, Cell Lineage, Developmental Gene Expression Regulation, Hematopoietic Stem Cells, Interferon-gamma, Mesonephros, Signal Transduction, Animals, Zebrafish
Source:Developmental Cell
ISSN:1534-5807
Publisher:Cell Press
Volume:31
Number:5
Page Range:640-653
Date:8 December 2014
Official Publication:https://doi.org/10.1016/j.devcel.2014.11.007
PubMed:View item in PubMed

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