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| Item Type: | Article |
|---|---|
| Title: | Interferon gamma signaling positively regulates hematopoietic stem cell emergence |
| Creators Name: | Sawamiphak, S., 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 |
| Additional Information: | Copyright © 2014 Elsevier Inc. All rights reserved. |
| Official Publication: | https://doi.org/10.1016/j.devcel.2014.11.007 |
| External Fulltext: | View full text on PubMed Central |
| PubMed: | View item in PubMed |
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