Department of Pharmacology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA.
Brain Res. 2010 Apr 23;1327:6-15. doi: 10.1016/j.brainres.2010.02.048. Epub 2010 Feb 20.
We have examined the expression and localization patterns of hyaluronan and hyaluronan-binding chondroitin sulfate proteoglycans in neural stem cells and differentiated neural cells derived from mouse embryonic stem cells. Expression of proteoglycans and hyaluronan was weak in the SSEA1-positive embryonic stem cells but increased noticeably after retinoic acid induction to nestin-positive neural stem cells. After subsequent plating, the hyaluronan-binding chondroitin sulfate proteoglycans aggrecan, neurocan, and versican are expressed by cells in both the astrocytic and neuronal lineages. During the time period that hyaluronan was present, it co-localized with each of the hyaluronan-binding proteoglycans studied and was found to be clearly associated with beta-III tubulin-expressing neurons and oligodendrocytes expressing the O4 sulfatide marker. Although proteoglycan expression levels increased to varying degrees following neural differentiation, they did not change noticably during the following 2 weeks in culture, but there was a significant decrease in hyaluronan expression. Our studies therefore demonstrate the expression by neural stem cells and neural cells derived from them of hyaluronan and its associated proteoglycans, thereby providing a necessary foundation for integrating their specific properties into developing strategies for therapeutic applications.
我们研究了透明质酸及其结合型硫酸软骨素蛋白聚糖在小鼠胚胎干细胞来源的神经干细胞和分化的神经细胞中的表达和定位模式。蛋白聚糖和透明质酸的表达在 SSEA1 阳性的胚胎干细胞中较弱,但在维甲酸诱导至巢蛋白阳性的神经干细胞后明显增加。随后进行铺板,透明质酸结合型硫酸软骨素蛋白聚糖 aggrecan、neurocan 和 versican 由星形胶质细胞和神经元谱系中的细胞表达。在透明质酸存在的期间,它与研究的每种透明质酸结合蛋白聚糖共定位,并与表达β-III 微管蛋白的神经元和表达 O4 硫酸软骨素标记的少突胶质细胞明显相关。尽管神经分化后蛋白聚糖的表达水平在不同程度上增加,但在随后的 2 周培养中并没有明显变化,但透明质酸的表达显著下降。因此,我们的研究表明神经干细胞及其衍生的神经细胞表达透明质酸及其相关蛋白聚糖,从而为整合它们的特性纳入治疗应用的发展策略提供了必要的基础。