Infection-responsive expansion of the hematopoietic stem and progenitor cell compartment in zebrafish is dependent upon inducible nitric oxide

Cell Stem Cell. 2012 Feb 3;10(2):198-209. doi: 10.1016/j.stem.2012.01.007.


Hematopoietic stem cells (HSCs) are rare multipotent cells that contribute to all blood lineages. During inflammatory stress, hematopoietic stem and progenitor cells (HSPCs) can be stimulated to proliferate and differentiate into the required immune cell lineages. Manipulating signaling pathways that alter HSPC capacity holds great promise in the treatment of hematological malignancies. To date, signaling pathways that influence HSPC capacity, in response to hematopoietic stress, remain largely unknown. Using a zebrafish model of demand-driven granulopoiesis to explore the HSPC response to infection, we present data supporting a model where the zebrafish ortholog of the cytokine-inducible form of nitric oxide synthase (iNOS/NOS2) Nos2a acts downstream of the transcription factor C/ebpβ to control expansion of HSPCs following infection. These results provide new insights into the reactive capacity of HSPCs and how the blood system is "fine-tuned" in response to inflammatory stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Hematopoietic Stem Cells / immunology*
  • Hematopoietic Stem Cells / microbiology*
  • Humans
  • Immunity, Innate
  • Inflammation / immunology
  • Inflammation / microbiology
  • Lymphocyte Depletion
  • Neutrophils / immunology*
  • Neutrophils / microbiology*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • Salmonella enterica / immunology
  • Signal Transduction
  • Zebrafish / growth & development
  • Zebrafish / immunology
  • Zebrafish / microbiology
  • Zebrafish Proteins / metabolism


  • CCAAT-Enhancer-Binding Protein-beta
  • Zebrafish Proteins
  • Nitric Oxide
  • Nitric Oxide Synthase Type II