PUBLICATION
Interferon Gamma Signaling Positively Regulates Hematopoietic Stem Cell Emergence
- Authors
- Sawamiphak, S., Kontarakis, Z., Stainier, D.Y.
- ID
- ZDB-PUB-141210-5
- Date
- 2014
- Source
- Developmental Cell 31: 640-653 (Journal)
- Registered Authors
- Kontarakis, Zacharias, Stainier, Didier
- Keywords
- none
- MeSH Terms
-
- Hematopoietic Stem Cells/cytology*
- Hematopoietic Stem Cells/metabolism*
- Mesonephros/cytology*
- Aorta/metabolism
- Interferon-gamma/metabolism*
- Signal Transduction*/physiology
- Gene Expression Regulation, Developmental/physiology*
- Animals
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Cell Lineage
- PubMed
- 25490269 Full text @ Dev. Cell
Citation
Sawamiphak, S., Kontarakis, Z., Stainier, D.Y. (2014) Interferon Gamma Signaling Positively Regulates Hematopoietic Stem Cell Emergence. Developmental Cell. 31:640-653.
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-γ (IFN-γ) 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-γ overexpression partially rescues the HSC loss observed in the absence of blood flow or Notch signaling. Importantly, IFN-γ signaling acts cell autonomously to control the endothelial-to-HSC transition. IFN-γ activates Stat3, an atypical transducer of IFN-γ 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping