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题名:The bioactive lipid sphingosylphosphorylcholine induces differentiation of mouse embryonic stem cells and human promyelocytic leukaemia cells
作者:Alexander Kleger, Tobias Busch, Stefan Liebau,
来源:Cellular Signalling, Volume 19, Issue 2, February 2007, Pages 367-377
URL :http://dx.doi.org/10.1016/j.cellsig.2006.07.015
日期:070115
摘要:Alexander Klegera, Tobias Buscha, Stefan Liebauf, Katja Prellec, Stephan Paschkeb, Michael Beila, Alexandra Rolletschekd, Anna Wobusd, Eckhard Wolfe, Guido Adlera and Thomas Seufferleina, ,

aDepartment of Internal Medicine I, Medical University of Ulm, Robert Koch Str. 8 D-89081 Ulm, Germany
bDepartment of Surgery, University of Ulm, Ulm, Germany
cSchering AG, Berlin, Germany
dLeibniz Institute (IPK) Gatersleben, Germany
eGene Center, Munich, Germany
fDepartment of Anatomy and Cell Biology, University of Ulm, Ulm, Germany

Received 18 June 2006; revised 18 July 2006; accepted 18 July 2006. Available online 28 July 2006.


Abstract

Sphingosylphosphorylcholine (SPC) is the major component of high-density lipoproteins (HDL) in blood plasma. The bioactive lipid acts mainly via G protein coupled receptors (GPCRs). Similar to ligands of other GPCRs, SPC has multiple biological roles including the regulation of proliferation, migration, angiogenesis, wound healing and heart rate. Lysophospholipids and their receptors have also been implicated in cell differentiation. A potential role of SPC in stem cell or tumour cell differentiation has been elusive so far. Here we examined the effect of SPC on the differentiation of mouse embryonic stem (ES) cells and of human NB4 promyelocytic leukemia cells, a well established tumour differentiation model. Our data show that mouse embryonic stem cells and NB4 cells express the relevant GPCRs for SPC. We demonstrate both at the level of morphology and of gene expression that SPC induces neuronal and cardiac differentiation of mouse ES cells. Furthermore, SPC induces differentiation of NB4 cells by a mechanism which is critically dependent on the activity of the MEK–ERK cascade. Thus, the bioactive lipid SPC is a novel differentiation inducing agent both for mouse ES cells, but also of certain human tumour cells.

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