胚胎干细胞中脂质磷酸盐磷酸酶-3 的缺乏会影响神经元分化和突起生长。
Lack of lipid phosphate phosphatase-3 in embryonic stem cells compromises neuronal differentiation and neurite outgrowth.
机构信息
Instituto de Fisiología Celular, División de Neurociencias, Universidad Nacional Autónoma de México.
出版信息
Dev Dyn. 2012 May;241(5):953-64. doi: 10.1002/dvdy.23779.
BACKGROUND
Bioactive lipids such as lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) have been recently described as important regulators of pluripotency and differentiation of embryonic stem (ES) cells and neural progenitors. Due to the early lethality of LPP3, an enzyme that regulates the levels and biological activities of the aforementioned lipids, it has been difficult to assess its participation in early neural differentiation and neuritogenesis.
RESULTS
We find that Ppap2b(-/-) (Lpp3(-/-) ) ES cells differentiated in vitro into spinal neurons show a considerable reduction in the amount of neural precursors and young neurons formed. In addition, differentiated Lpp3(-/-) neurons exhibit impaired neurite outgrowth. Surprisingly, when Lpp3(-/-) ES cells were differentiated, an unexpected appearance of smooth muscle actin-positive cells was observed, an event that was partially dependent upon phosphorylated sphingosines.
CONCLUSIONS
Our data show that LPP3 plays a fundamental role during spinal neuron differentiation from ES and that it also participates in regulating neurite and axon outgrowth.
背景
溶血磷脂酸（LPA）和鞘氨醇-1-磷酸（S1P）等生物活性脂质最近被描述为胚胎干细胞（ES）和神经祖细胞多能性和分化的重要调节因子。由于调节上述脂质水平和生物学活性的酶 LPP3 具有早期致死性，因此很难评估其在早期神经分化和神经突生成中的参与。
结果
我们发现体外分化的 Pap2b(-/-)（Lpp3(-/-)）ES 细胞形成的神经前体细胞和年轻神经元数量明显减少。此外，分化的 Lpp3(-/-)神经元表现出神经突生长受损。令人惊讶的是，当 Lpp3(-/-)ES 细胞分化时，观察到平滑肌肌动蛋白阳性细胞的意外出现，这一事件部分依赖于磷酸化鞘氨醇。
结论
我们的数据表明，LPP3 在 ES 来源的脊髓神经元分化过程中发挥着重要作用，并且它还参与调节神经突和轴突的生长。
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