PUBLICATION

Proinflammatory signaling regulates hematopoietic stem cell emergence

Authors
Espín-Palazón, R., Stachura, D.L., Campbell, C.A., García-Moreno, D., Del Cid, N., Kim, A.D., Candel, S., Meseguer, J., Mulero, V., Traver, D.
ID
ZDB-PUB-161220-10
Date
2014
Source
Cell   159: 1070-85 (Journal)
Registered Authors
Espín-Palazón, Raquel, Mulero, Victor, Traver, David
Keywords
none
MeSH Terms
  • Neutrophils/metabolism
  • Animals
  • Tumor Necrosis Factor-alpha/metabolism
  • Embryo, Nonmammalian/metabolism
  • Signal Transduction*
  • Receptors, Notch/metabolism
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism*
  • NF-kappa B/metabolism
  • Hematopoiesis
  • Zebrafish/metabolism
(all 11)
PubMed
25416946 Full text @ Cell
Abstract
Hematopoietic stem cells (HSCs) underlie the production of blood and immune cells for the lifetime of an organism. In vertebrate embryos, HSCs arise from the unique transdifferentiation of hemogenic endothelium comprising the floor of the dorsal aorta during a brief developmental window. To date, this process has not been replicated in vitro from pluripotent precursors, partly because the full complement of required signaling inputs remains to be determined. Here, we show that TNFR2 via TNF? activates the Notch and NF-?B signaling pathways to establish HSC fate, indicating a requirement for inflammatory signaling in HSC generation. We determine that primitive neutrophils are the major source of TNF?, assigning a role for transient innate immune cells in establishing the HSC program. These results demonstrate that proinflammatory signaling, in the absence of infection, is utilized by the developing embryo to generate the lineal precursors of the adult hematopoietic system.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
bw9TgTransgenic Insertion
    cz1TgTransgenic Insertion
      gl22TgTransgenic Insertion
        i114TgTransgenic Insertion
          jh11TgTransgenic Insertion
            kca3TgTransgenic Insertion
              kca4TgTransgenic Insertion
                la2TgTransgenic Insertion
                  nc1TgTransgenic Insertion
                    nkuasrfp1aTgTransgenic Insertion
                      1 - 10 of 18
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                      Human Disease / Model
                      Sequence Targeting Reagents
                      Fish
                      Antibodies
                      Orthology
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GAL4EFGGAL4
                      GAL4FFEFGGAL4FF
                      GFPEFGGFP
                      mCherryEFGmCherry
                      RFPEFGRFP
                      1 - 7 of 7
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                      Citation
                      Espín-Palazón, R., Stachura, D.L., Campbell, C.A., García-Moreno, D., Del Cid, N., Kim, A.D., Candel, S., Meseguer, J., Mulero, V., Traver, D. (2014) Proinflammatory signaling regulates hematopoietic stem cell emergence. Cell. 159:1070-85.