PUBLICATION

Thrombin Receptor Regulates Hematopoiesis and Endothelial-to-Hematopoietic Transition

Authors
Yue, R., Li, H., Liu, H., Li, Y., Wei, B., Gao, G., Jin, Y., Liu, T., Wei, L., Du, J., and Pei, G.
ID
ZDB-PUB-120424-23
Date
2012
Source
Developmental Cell   22(5): 1092-1100 (Journal)
Registered Authors
Du, Jiu Lin, Jin, Yi
Keywords
none
MeSH Terms
  • Amides/pharmacology
  • Zebrafish/blood
  • Zebrafish/physiology*
  • Receptors, Thrombin/antagonists & inhibitors
  • Receptors, Thrombin/genetics
  • Receptors, Thrombin/metabolism*
  • Hematopoiesis/physiology*
  • Pyrroles/pharmacology
  • Flow Cytometry
  • rho-Associated Kinases/antagonists & inhibitors
  • rho-Associated Kinases/metabolism
  • Embryonic Stem Cells/cytology
  • Embryonic Stem Cells/metabolism
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism*
  • Quinazolines/pharmacology
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism*
  • Cells, Cultured
  • Animals
  • Pyridines/pharmacology
  • rhoA GTP-Binding Protein/antagonists & inhibitors
  • rhoA GTP-Binding Protein/metabolism
  • Cell Differentiation/physiology*
  • Mice
(all 25)
PubMed
22521721 Full text @ Dev. Cell
Abstract

Hematopoietic development and vascular development are closely related physiological processes during vertebrate embryogenesis. Recently, endothelial-to-hematopoietic transition (EHT) was demonstrated to be critical for hematopoietic stem and progenitor cell induction, but its underlying regulatory mechanisms remain poorly understood. Here we show that thrombin receptor (F2r), a protease-activated G protein-coupled receptor required for vascular development, functions as a negative regulator during hematopoietic development. F2r is significantly upregulated during hematopoietic differentiation of mouse embryonic stem cells (mESCs) and zebrafish hematopoietic development. Pharmacological or genetic inhibition of F2r promotes hematopoietic differentiation, whereas F2r overexpression shows opposite effects. Further mechanistic studies reveal that F2r-RhoA/ROCK pathway inhibits EHT in vitro and negatively regulates zebrafish EHT and hematopoietic stem cell induction in vivo. Taken together, this study demonstrates a fundamental role of F2r-RhoA/ROCK pathway in vertebrate hematopoiesis and EHT, as well as an important molecular mechanism coordinating hematopoietic and vascular development.

Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
la4TgTransgenic Insertion
    rj2TgTransgenic Insertion
      rj6TgTransgenic Insertion
        s843TgTransgenic Insertion
          zf169TgTransgenic Insertion
            1 - 5 of 5
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Fish
            Antibodies
            No data available
            Orthology
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            Engineered Foreign Genes
            Marker Marker Type Name
            DsRedEFGDsRed
            EGFPEFGEGFP
            RFPEFGRFP
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            Mapping