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

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.