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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2015     Display Documents



ID: 711865.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2015
Interferon gamma signaling positively regulates hematopoietic stem cell emergence
Authors:Sawamiphak, S.; Kontarakis, Z.; Stainier, D. Y.
Date of Publication (YYYY-MM-DD):2014-12-08
Title of Journal:Dev Cell
Volume:31
Issue / Number:5
Start Page:640
End Page:653
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Animals; Aorta/metabolism; Cell Lineage; Gene Expression Regulation, Developmental/*physiology; Hematopoietic Stem Cells/*cytology/*metabolism; Interferon-gamma/*metabolism; Mesonephros/*cytology; *Signal Transduction/physiology; Zebrafish/embryology/genetics/*metabolism
External Publication Status:published
Document Type:Article
Communicated by:MPI für Herz- und Lungenforschung
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany. Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany. Electronic address: didier.stainier@mpi-bn.mpg.de. %^ 1435821975
Identifiers:ISSN:1878-1551 (Electronic) 1534-5807 (Linking) %R 10.1016/j.devcel.2014.11.007
URL:http://www.ncbi.nlm.nih.gov/pubmed/25490269
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