PUBLICATION

SUMO1-activating enzyme subunit 1 is essential for the survival of hematopoietic stem/progenitor cells in zebrafish

Authors
Li, X., Lan, Y., Xu, J., Zhang, W., and Wen, Z.
ID
ZDB-PUB-121121-32
Date
2012
Source
Development (Cambridge, England)   139(23): 4321-4329 (Journal)
Registered Authors
Wen, Zilong
Keywords
zebrafish, hematopoiesis, SUMO-activating enzyme subunit 1
MeSH Terms
  • Animals
  • Sumoylation
  • Aorta/embryology
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Apoptosis/genetics
  • Humans
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/physiology*
  • HEK293 Cells
  • Cell Proliferation
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Hematopoietic System/embryology*
  • SUMO-1 Protein/genetics
  • SUMO-1 Protein/metabolism*
  • Hematopoiesis/genetics*
  • Morpholinos/genetics
  • Mutation
  • Cell Differentiation
  • Cell Line
  • Cell Movement
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
(all 24)
PubMed
23132242 Full text @ Development
Abstract

In vertebrates, establishment of the hematopoietic stem/progenitor cell (HSPC) pool involves mobilization of these cells in successive developmental hematopoietic niches. In zebrafish, HSPCs originate from the ventral wall of the dorsal aorta (VDA), the equivalent of the mammalian aorta-gonad-mesonephros (AGM). The HSPCs subsequently migrate to the caudal hematopoietic tissue (CHT) for transitory expansion and differentiation during the larval stage, and they finally colonize the kidney, where hematopoiesis takes place in adult fish. Here, we report the isolation and characterization of a zebrafish mutant, tangohkz5, which shows defects of definitive hematopoiesis. In tangohkz5 mutants, HSPCs initiate normally in the AGM and subsequently colonize the CHT. However, definitive hematopoiesis is not sustained in the CHT owing to accelerated apoptosis and diminished proliferation of HSPCs. Positional cloning reveals that tangohkz5 encodes SUMO1-activating enzyme subunit 1 (Sae1). A chimera generation experiment and biochemistry analysis reveal that sae1 is cell-autonomously required for definitive hematopoiesis and that the tangohkz5 mutation produces a truncated Sae1 protein (”ΔSae1), resulting in systemic reduction of sumoylation. Our findings demonstrate that sae1 is essential for the maintenance of HSPCs during fetal hematopoiesis in zebrafish.

Genes / Markers
Figures
Figure Gallery (9 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hkz5
    Point Mutation
    la2TgTransgenic Insertion
      y1TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        ube2ibMO1-ube2ibMRPHLNO
        1 - 1 of 1
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        Fish
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab1-mycmonoclonal
          IgG1Mouse
          Ab1-sumopolyclonal
            Rabbit
            Ab1-sumo1polyclonal
              Rabbit
              1 - 3 of 3
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              Orthology
              Gene Orthology
              sae1
              1 - 1 of 1
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              Engineered Foreign Genes
              Marker Marker Type Name
              EGFPEFGEGFP
              1 - 1 of 1
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              Mapping
              No data available