title: The bioactive lipid sphingosylphosphorylcholine induces differentiation of mouse embryonic stem cells and human promyelocytic leukaemia cells.
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.
authors.affiliation: Department of Internal Medicine I, Medical University of Ulm, Robert Koch Strasse 8, D-89081 Ulm, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kleger
authors.forename: Tobias
authors.initials: T
authors.lastname: Busch
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebau
authors.forename: Katja
authors.initials: K
authors.lastname: Prelle
authors.forename: Stephan
authors.initials: S
authors.lastname: Paschke
authors.forename: Michael
authors.initials: M
authors.lastname: Beil
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rolletschek
authors.forename: Anna
authors.initials: A
authors.lastname: Wobus
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Guido
authors.initials: G
authors.lastname: Adler
authors.forename: Thomas
authors.initials: T
authors.lastname: Seufferlein
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D022001:Focal Adhesions; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D051379:Mice; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000199:Actins; D043562:Receptors, G-Protein-Coupled; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D048049:Extracellular Signal-Regulated MAP Kinases; D013110:Sphingosine