Stromal cell-derived factor 1 is secreted by meningeal cells and acts as chemotactic factor on neuronal stem cells of the cerebellar external granular layer
Stromal cell-derived factor 1 is secreted by meningeal cells and acts as chemotactic factor on neuronal stem cells of the cerebellar external granular layer
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DOI：
10.1016/s0306-4522(02)00307-x
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发表时间：
2002-01-01
期刊：
影响因子：
3.3
通讯作者：
Hartmann, D
中科院分区：
文献类型：
--
作者：
Reiss, K;Mentlein, R;Hartmann, D
小脑外颗粒层 (EGL) 是一个异常持久的神经增殖区，位于软脑膜表面正下方。它的位置和稳定性很大程度上取决于脑膜细胞，因为它们的选择性破坏导致其快速分散，形成大规模的皮质异位。最近，类似的异位被描述为基质细胞衍生因子 1 (SDF-1) 缺乏的副作用，基质细胞衍生因子 1 是造血前体细胞迁移的化学引诱剂。在这里，我们证明 SDF-1 存在于体内和体外的脑膜细胞中，并以功能相关的浓度分泌到培养基中。相应地，SDF-1 受体（称为 CXCR4）可以在外部颗粒层的干细胞上得到证实，但在开始最终向内迁移的有丝分裂后细胞中不存在。我们表明，SDF-1 被 EGL 中高度表达的硫酸乙酰肝素蛋白多糖以层流方式浓缩，因此可能以一种阶梯梯度局部限制 SDF-1 对 EGL 的作用。在体外，SDF-1 趋化性地吸引从外部分离的神经元细胞，但不吸引从内部颗粒层分离的神经元细胞，在博伊登室测定中，其浓度在脑膜细胞条件培养基中发现。通过免疫沉淀从条件培养基中选择性去除 SDF-1 可消除其化学吸引作用，并可通过添加重组 SDF-1 再次重建。因此，脑膜细胞是大脑发育过程中 SDF-1 表达的重要来源，与它在造血中的作用相比，SDF-1 似乎是吸引前体细胞进入其增殖室的关键因素。 (C) 2002 国际广播组织。由爱思唯尔科学有限公司出版。保留所有权利。
The cerebellar external granular layer (EGL) is an unusually long-lasting neural proliferative zone positioned immediately beneath the pial surface. Its position and stability critically depend on meningeal cells, as their selective destruction leads to its rapid dispersal, creating massive cortical ectopia. Similar ectopias have recently been described as a side effect of deficiency for stromal cell-derived factor 1 (SDF-1), a chemoattractant for haematopoietic precursor cell migration. Here we show that SDF-1 is present in meningeal cells in vivo and in vitro, where it is secreted in functionally relevant concentrations into the medium. Correspondingly, the SDF-1 receptor (termed CXCR4) can be demonstrated on stem cells of the external granular layer, but is absent on postmitotic cells commencing their final inward migration. We show that SDF-1 is concentrated by heparan sulphate proteoglycans highly expressed in the EGL in a laminar fashion, which thus might act to locally restrict SDF-1 action to the EGL in a kind of step gradient. In vitro, SDF-1 chemotactically attracts neuronal cells isolated from the external, but not from the internal granular layer, in a Boyden chamber assay in concentrations found in meningeal cell-conditioned medium. Selective removal of SDF-1 from conditioned media by immunoprecipitation abolishes their chemoattractive action, which can be reconstituted again by the addition of recombinant SDF-1. Meningeal cells are thus an important source for the expression of SDF-1 during brain development, which - comparable to its role in haematopoiesis - appears to be a key factor attracting precursor cells to their proliferative compartment. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.