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进展编译——Nature:神经干细胞的可塑性

躯体干细胞被认为具有广阔的分化潜力(这里指可塑性),通过混合细胞培养实验将干细胞暴露在其他谱系的细胞外基质发育信号条件下。最近,支持干细胞可塑性存在的观点被一系列的实验证据驳倒,因为干细胞表达其他谱系的功能特征被认为通过细胞融合介导的谱系特征遗传决定子(染色体DNA)的方式获得而不是通过信号介导的分化。本研究中,我们将可以转变为神经元和神经胶质细胞的鼠神经干细胞与能够形成血管的人的内皮细胞共培养。我们观察到和内皮细胞共培养后,6%的神经干细胞转变为不表达神经细胞和神经胶质细胞标志物的细胞,反而稳定地表达多个内皮细胞标志物,并且具有形成血管网的能力。这是非常令人惊讶的,因为神经干细胞与内皮细胞分别发育自外胚层和中胚层。在与活的神经干细胞共培养前内皮细胞通过固定被杀死(防止细胞融合)和染色体核型分析实验显示,神经干细胞分化成为内皮细胞样细胞不是通过细胞融合。我们得出结论,干细胞可塑性是神经干细胞真实的特性,神经干细胞不通过细胞融合可以转化为预想不到的细胞类型。

Nature 430, 350 - 356 (15 July 2004); doi:10.1038/nature02604

Cell fusion-independent differentiation of neural stem cells to the endothelial lineage

Somatic stem cells have been claimed to possess an unexpectedly broad differentiation potential (referred to here as plasticity) that could be induced by exposing stem cells to the extracellular developmental signals of other lineages in mixed-cell cultures. Recently, this and other experimental evidence supporting the existence of stem-cell plasticity have been refuted because stem cells have been shown to adopt the functional features of other lineages by means of cell-fusion-mediated acquisition of lineage-specific determinants (chromosomal DNA) rather than by signal-mediated differentiation. In this study we co-cultured mouse neural stem cells (NSCs), which are committed to become neurons and glial cells, with human endothelial cells, which form the lining of blood vessels. We show that in the presence of endothelial cells six per cent of the NSC population converted to cells that did not express neuronal or glial markers, but instead showed the stable expression of multiple endothelial markers and the capacity to form capillary networks. This was surprising because NSCs and endothelial cells are believed to develop from the ectoderm and mesoderm, respectively. Experiments in which endothelial cells were killed by fixation before co-culture with live NSCs (to prevent cell fusion) and karyotyping analyses, revealed that NSCs had differentiated into endothelial-like cells independently of cell fusion. We conclude that stem-cell plasticity is a true characteristic of NSCs and that the conversion of NSCs to unanticipated cell types can be accomplished without cell fusion. [标签:content1][标签:content2]

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作者:admin@医学,生命科学    2011-03-26 17:14
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