Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology.
Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology.
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DOI：
10.1186/1471-2202-9-118
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发表时间：
2008-12-11
期刊：
影响因子：
2.4
通讯作者：
Hooks SB
中科院分区：
文献类型：
--
作者：
Hurst JH;Mumaw J;Machacek DW;Sturkie C;Callihan P;Stice SL;Hooks SB
溶血磷脂调节神经元、神经细胞系和神经前体细胞的形态和生长。目前还没有稳定的人类神经前体细胞株来研究溶血磷脂在人类神经发育中的作用。我们最近建立了一个稳定的、贴壁的人胚胎干细胞源性神经上皮细胞系(HES-NEP)，它概括了从胎儿组织中分离的神经前体细胞的形态和表型特征。这项研究的目的是确定HES-NEP细胞是否表达功能性溶血磷脂受体，以及这些受体的激活是否介导了对神经发育至关重要的细胞反应。我们的结果表明，溶血磷脂酸(LPA)和鞘氨醇-1-磷酸(S1P)受体在HES-NEP细胞中有功能表达，并与多种细胞信号通路相偶联。我们发现，在胚胎干细胞向HES-NEP的转变过程中，S1P1受体的转录水平显著增加。HES-NEP细胞表达LPA和S1P受体，与Gi/o G-蛋白偶联，抑制腺苷环化酶和Gq样磷脂酶C的活性。LPA和S1P还可通过依赖于表皮生长因子受体(EGFR)和ERK的Gi/o偶联受体，诱导p44/42ERK丝裂原活化，从而刺激细胞增殖。相反，LPA和S1P刺激瞬时细胞圆整和聚集，这种聚集不依赖于EGFR和ERK，但依赖于Rho效应器p160岩石。因此，溶血磷脂通过不同的机制调节神经前体细胞的生长和形态。这些发现建立了人类ES细胞来源的NEP细胞作为研究溶血磷脂在神经前体细胞中的作用的模型系统。
Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP) cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development. Our results demonstrate that Lysophosphatidic Acid (LPA) and Sphingosine-1-phosphate (S1P) receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown that transcript levels for S1P1 receptor increased significantly in the transition from embryonic stem cell to hES-NEP. hES-NEP cells express LPA and S1P receptors coupled to Gi/o G-proteins that inhibit adenylyl cyclase and to Gq-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via Gi/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR)- and ERK-dependent pathway. In contrast, LPA and S1P stimulate transient cell rounding and aggregation that is independent of EGFR and ERK, but dependent on the Rho effector p160 ROCK. Thus, lysophospholipids regulate neural progenitor growth and morphology through distinct mechanisms. These findings establish human ES cell-derived NEP cells as a model system for studying the role of lysophospholipids in neural progenitors.
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