PUBLICATION

Pivotal role of Pten in the balance between proliferation and differentiation of hematopoietic stem cells in zebrafish

Authors
Choorapoikayil, S., Kers, R., Herbomel, P., Kissa, K., and den Hertog, J.
ID
ZDB-PUB-131115-12
Date
2014
Source
Blood : (Unknown)
Registered Authors
Choorapoikayil, Suma, den Hertog, Jeroen, Herbomel, Philippe, Kissa-Marin, Karima
Keywords
none
MeSH Terms
  • Signal Transduction/drug effects
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Animals
  • Phosphatidylinositol 3-Kinases/antagonists & inhibitors
  • PTEN Phosphohydrolase/genetics*
  • PTEN Phosphohydrolase/metabolism*
  • Neutrophils/cytology
  • Neutrophils/metabolism
  • Cell Differentiation/drug effects
  • Cell Differentiation/genetics*
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/drug effects
  • Hematopoietic Stem Cells/metabolism*
  • Morpholines/pharmacology
  • Mutation
  • Gene Knockout Techniques
  • Hematopoiesis/genetics
  • Cell Proliferation/drug effects
  • Chromones/pharmacology
  • Cell Lineage/genetics
  • Animals, Genetically Modified
(all 23)
PubMed
24124088 Full text @ Blood
Abstract

Self-renewing hematopoietic stem/progenitor cells (HSPCs) produce blood cells of all lineages throughout life. PTEN, a tumor suppressor that antagonizes PI3-Kinase (PI3K) signaling, is frequently mutated in hematologic malignancies such as bone marrow failure and leukemia. We set out to investigate if Pten is required for hematopoiesis. Analysis of zebrafish mutants lacking functional Pten revealed that HSPCs colonized the caudal hematopoietic tissue (CHT) normally. There, HSPCs hyperproliferated and engaged in all blood lineages. However, they failed to differentiate into mature blood cells. Hence, Pten mutant zebrafish embryos displayed hallmarks of leukemia in humans. Inhibition of PI3K signaling in mutants lacking functional Pten suppressed hyperproliferation and released the differentiation arrest. We conclude that Pten has an essential role in the balance between proliferation and differentiation of blood cells.

Genes / Markers
Figures
No images available
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu1435
    Point Mutation
    hu1864
      Point Mutation
      la2TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        Sequence Targeting Reagents
        No data available
        Fish
        Antibodies
        Orthology
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
        Show
        Mapping