The bioactive lipid sphingosylphosphorylcholine induces differentiation of mouse embryonic stem cells and human promyelocytic leukaemia cells
The bioactive lipid sphingosylphosphorylcholine induces differentiation of mouse embryonic stem cells and human promyelocytic leukaemia cells
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DOI：
10.1016/j.cellsig.2006.07.015
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发表时间：
2007-02-01
影响因子：
4.8
通讯作者：
Seufferlein, Thomas
中科院分区：
文献类型：
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作者：
Kleger, Alexander;Busch, Tobias;Seufferlein, Thomas
sphingosylphospylcholine （SPC）是血浆中高密度脂蛋白（HDL）的主要成分。生物活性脂质主要通过G蛋白偶联受体（gpcr）起作用。与其他gpcr配体类似，SPC具有多种生物学作用，包括调节增殖、迁移、血管生成、伤口愈合和心率。溶血磷脂及其受体也与细胞分化有关。到目前为止，SPC在干细胞或肿瘤细胞分化中的潜在作用一直难以捉摸。在这里，我们研究了SPC对小鼠胚胎干细胞（ES）细胞和人NB4早幼粒细胞白血病细胞（一种成熟的肿瘤分化模型）分化的影响。我们的数据表明，小鼠胚胎干细胞和NB4细胞表达与SPC相关的gpcr。我们在形态学和基因表达水平上证明了SPC诱导小鼠胚胎干细胞的神经元和心脏分化。此外，SPC通过一种严重依赖于MEK-ERK级联活性的机制诱导NB4细胞分化。因此，具有生物活性的脂质SPC是一种新的分化诱导剂，不仅适用于小鼠胚胎干细胞，也适用于某些人类肿瘤细胞。(c) 2006爱思唯尔公司版权所有。
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. (c) 2006 Elsevier Inc. All rights reserved.