Thrombin Receptor: Grasps Endothelial to Hematopoietic Cell Transition
Source:
Time: 2012-05-02
Endothelial-to-hematopoietic transition (EHT) is a novel type of cell transition that is essential for hematopoietic stem and progenitor cell (HSPC) induction. HSPCs derive directly from hemogenic endothelial cells during early development, without apparent signs of asymmetric cell division. Although the transcription factor Runx1 is shown to be required for EHT, extracellular factors or signal pathways regulating this process still remain poorly understood. Recently, a research group led by Prof. PEI Gang at the Shanghai Institute of Biochemistry and Cell Biology, CAS, discovered that thrombin receptor plays a critical role in vertebrate hematopoiesis through regulating EHT..
In this study, Dr. YUE Rui and his colleagues used bioinformatic tools to identify that thrombin receptor (F2r or PAR1), a G protein-couple receptor critically involved in coagulation and vascular development, is significantly up-regulated during hematopoietic differentiation of mouse embryonic stem cells (mESCs). Next, they carried out pharmacological and genetic modulation of F2r signaling during hematopoietic differentiation and zebrafish embryogenesis and found that it is a negative regulator of hematopoiesis both in vitro and in vivo. Mechanistic studies revealed that RhoA/ROCK pathway, a negative regulator of epithelial-to-mesenchymal transition (EMT), mediates the downstream effects of F2r, regulating tight junction dissolution of hemogenic endothelial cells and EHT.
This work entitled “Thrombin Receptor Regulates Hematopoiesis and Endothelial-to-Hematopoietic Transition” was published online in Developmental Cell on April 19th, 2012.
This study was supported by grants from the Ministry of Science and Technology, Chinese Academy of Sciences and Shanghai Institutes for Biological Sciences.
AUTHOR CONTACT:
PEI Gang
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
F2r-RhoA/ROCK pathway activation inhibits tight junction dissolution in hemogenic endothelial cells, whereas pharmacological or genetic blockage of F2r reverses the inhibition, accelerating EHT and HSPC induction (Image provided by Dr. PEI Gang).
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