Identification and functions of chondroitin sulfate in the milieu of neural stem cells
Identification and functions of chondroitin sulfate in the milieu of neural stem cells
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DOI：
10.1074/jbc.m507130200
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发表时间：
2006-03-03
影响因子：
4.8
通讯作者：
Oohira, A
中科院分区：
文献类型：
--
作者：
Ida, M;Shuo, T;Oohira, A
细胞的行为通常被认为是受环境因素的调控，但对神经干细胞环境中的分子研究很少。我们通过免疫组织化学发现，胚胎第14天大鼠端脑心室区巢蛋白阳性细胞或神经干/祖细胞周围存在硫酸软骨素（CS）。在脑室区检测到脑特异性硫酸软骨素蛋白聚糖（CSPG），包括神经聚糖、磷酸蛋白聚糖/受体型蛋白酪氨酸磷酸酶β和神经聚糖C。由胎儿端脑细胞形成的神经球也表达这些CSPGs和NG 2蛋白聚糖。为了研究CS多糖在神经干细胞环境中的结构特征和功能，我们从胚胎第14天的端脑中分离和纯化CS。CS制剂由硫酸化的大小和程度不同的两个部分组成：硫酸化程度低的小CS多糖和硫酸化程度高的大CS多糖。有趣的是，CS多糖和商业制剂硫酸皮肤素CS-B和E型的高度硫酸化CS促进成纤维细胞生长因子-2介导的神经干/祖细胞增殖。这些CS制剂都没有促进表皮生长因子介导的神经干细胞增殖。这些结果表明，这些CSPGs作为一组细胞微环境因子参与神经干细胞的增殖。
The behavior of cells is generally considered to be regulated by environmental factors, but the molecules in the milieu of neural stem cells have been little studied. We found by immunohistochemistry that chondroitin sulfate (CS) existed in the surroundings of nestin-positive cells or neural stem/progenitor cells in the rat ventricular zone of the telencephalon at embryonic day 14. Brain-specific chondroitin sulfate proteoglycans (CSPGs), including neurocan, phosphacan/receptor-type protein-tyrosine phosphatase beta, and neuroglycan C, were detected in the ventricular zone. Neurospheres formed by cells from the fetal telencephalon also expressed these CSPGs and NG2 proteoglycan. To examine the structural features and functions of CS polysaccharides in the milieu of neural stem cells, we isolated and purified CS from embryonic day 14 telencephalons. The CS preparation consisted of two fractions differing in size and extent of sulfation: small CS polysaccharides with low sulfation and large CS polysaccharides with high sulfation. Interestingly, both CS polysaccharides and commercial preparations of dermatan sulfate CS-B and an E-type of highly sulfated CS promoted the fibroblast growth factor-2-mediated proliferation of neural stem/progenitor cells. None of these CS preparations promoted the epidermal growth factor-mediated neural stem cell proliferation. These results suggest that these CSPGs are involved in the proliferation of neural stem cells as a group of cell microenvironmental factors.