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
  • Mesonephros/cytology*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Gene Expression Regulation, Developmental/physiology*
  • Cell Lineage
  • Aorta/metabolism
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/metabolism*
  • Interferon-gamma/metabolism*
  • Signal Transduction*/physiology
  • Animals
(all 12)
PubMed
25490269 Full text @ Dev. Cell
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
Figures
Figure Gallery (9 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f12TgTransgenic Insertion
    f13TgTransgenic Insertion
      kca3TgTransgenic Insertion
        kca4TgTransgenic Insertion
          la2TgTransgenic Insertion
            mu101TgTransgenic Insertion
              s896TgTransgenic Insertion
                s939TgTransgenic Insertion
                  s986
                    Indel
                    s987
                      Small Deletion
                      1 - 10 of 11
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      ifng1MO1-ifng1MRPHLNO
                      ifngr1MO2-ifngr1MRPHLNO
                      ifngr1TALEN1-ifngr1TALEN
                      mib1MO4-mib1MRPHLNO
                      tnnt2aMO1-tnnt2aMRPHLNO
                      1 - 5 of 5
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                      Fish
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CeruleanEFGCerulean
                      EGFPEFGEGFP
                      GAL4EFGGAL4
                      GAL4FFEFGGAL4FF
                      mCherryEFGmCherry
                      RFPEFGRFP
                      YFPEFGYFP
                      1 - 7 of 7
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                      Mapping
                      No data available