Infection-responsive expansion of the hematopoietic stem and progenitor cell compartment in zebrafish is dependent upon inducible nitric oxide.
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.
Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Christopher J
CJ
Hall
Maria Vega
MV
Flores
Stefan H
SH
Oehlers
Leslie E
LE
Sanderson
Enid Y
EY
Lam
Kathryn E
KE
Crosier
Philip S
PS
Crosier
D000818:Animals; D030801:Animals, Genetically Modified; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D008212:Lymphocyte Depletion; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019779:Salmonella enterica / Q000276:immunology; D015398:Signal Transduction; D015027:Zebrafish / Q000254:growth & development / Q000276:immunology / Q000382:microbiology; D029961:Zebrafish Proteins / Q000378:metabolism
D022782:CCAAT-Enhancer-Binding Protein-beta; D029961:Zebrafish Proteins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II