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独特的473HD-硫酸软骨素表位由放射状胶质细胞表达,并参与神经前体细胞增殖。

The unique 473HD-Chondroitinsulfate epitope is expressed by radial glia and involved in neural precursor cell proliferation.

作者信息

von Holst Alexander, Sirko Swetlana, Faissner Andreas

机构信息

Cell Morphology and Molecular Neurobiology, Faculty of Biology, Ruhr-University Bochum, D-44780 Bochum, Germany.

出版信息

J Neurosci. 2006 Apr 12;26(15):4082-94. doi: 10.1523/JNEUROSCI.0422-06.2006.

Abstract

Neural stem cells have been documented in both the developing and the mature adult CNSs of mammals. This cell population holds a considerable promise for therapeutical applications in a wide array of CNS diseases. Therefore, universally applicable strategies for the purification of this population to further its cell biological characterization are sought. Here, we report that the unique chondroitin sulfate epitope recognized by the monoclonal antibody 473HD is surface expressed on actively cycling, multipotent progenitor cells of the developing telencephalon with radial glia-like properties. When used for immunopanning, the antibody enriched at least threefold for neural stem/progenitor cells characterized by the ability to self-renew as neurospheres that generated all major neural lineages in differentiation assays. In contrast, the 473HD-depleted cell fraction was mostly devoid of neurosphere-forming cells. The isolation of 473HD-positive adult multipotent progenitors from the subependymal zone of the lateral ventricle wall revealed a substantial overlap with the known adult neural stem cell marker LewisX. When the chondroitin sulfates were removed from immunoselected 473HD-positive neural stem/progenitor cell surfaces by chondroitinase ABC treatment or perturbed by the monoclonal antibody 473HD that recognizes the unique DSD-1 chondroitin sulfate epitope, the generation of neurospheres was significantly reduced. Thus, the 473HD epitope could not only be used for the isolation of multipotent neural progenitors during forebrain development as well as from the adult neurogenic niche but may also constitute a functionally important entity of the neural stem cell niche.

摘要

神经干细胞已在哺乳动物发育中的和成熟的中枢神经系统中被记录下来。这群细胞在多种中枢神经系统疾病的治疗应用方面具有巨大潜力。因此,人们在寻找普遍适用的策略来纯化这群细胞,以进一步进行其细胞生物学特性研究。在此,我们报告单克隆抗体473HD识别的独特硫酸软骨素表位在发育中的端脑具有放射状胶质样特性的活跃增殖多能祖细胞表面表达。当用于免疫淘选时,该抗体使神经干细胞/祖细胞富集了至少三倍,这些细胞的特征是能够自我更新形成神经球,在分化实验中能产生所有主要神经谱系。相比之下,473HD耗尽的细胞部分大多没有形成神经球的细胞。从侧脑室壁室管膜下区分离473HD阳性的成年多能祖细胞发现,它与已知的成年神经干细胞标志物LewisX有大量重叠。当通过硫酸软骨素酶ABC处理从免疫选择的473HD阳性神经干细胞/祖细胞表面去除硫酸软骨素,或用识别独特的DSD-1硫酸软骨素表位的单克隆抗体473HD干扰时,神经球的生成显著减少。因此,473HD表位不仅可用于在前脑发育过程中以及从成年神经发生微环境中分离多能神经祖细胞,还可能构成神经干细胞微环境中一个功能重要的实体。

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