Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling
Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling
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DOI：
10.1523/jneurosci.2246-06.2006
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发表时间：
2006-09-27
影响因子：
5.3
通讯作者：
Hudson, Lynn D.
中科院分区：
文献类型：
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作者：
Nielsen, Joseph A.;Maric, Dragan;Hudson, Lynn D.
少突胶质细胞从祖细胞分化为髓鞘细胞时经历广泛的变化。为了更好地了解这种转化背后的分子机制，我们使用 A2B5 (+) 少突胶质细胞祖细胞和 O4 (+) 少突胶质细胞的基因表达谱进行了比较分析。使用流式细胞术对出生后大鼠脑中的细胞进行离体分类纯化。使用 Affymetrix 微阵列，鉴定出 1707 个转录物在 O4 (+) 少突胶质细胞中的表达增加了两倍以上。少突胶质细胞分化所需的许多基因在 O4 (+) 少突胶质细胞中上调，包括许多编码髓磷脂蛋白的基因。转录变化包括细胞粘附、肌动蛋白细胞骨架调节以及脂肪酸和胆固醇生物合成所需的基因。在 O4 (+) 阶段，一种新型富含脯氨酸的跨膜蛋白 (Prmp) 的表达增加。 Prmp 定位于质膜，表现出粘附特性，这对于连接细胞外基质与肌动蛋白细胞骨架可能很重要。总之，我们的结果强调了这种发现驱动的实验策略在识别与少突胶质细胞分化和髓鞘形成相关的基因方面的有用性。
Oligodendrocytes undergo extensive changes as they differentiate from progenitors into myelinating cells. To better understand the molecular mechanisms underlying this transformation, we performed a comparative analysis using gene expression profiling of A2B5 (+) oligodendrocyte progenitors and O4 (+) oligodendrocytes. Cells were sort-purified ex vivo from postnatal rat brain using flow cytometry. Using Affymetrix microarrays, 1707 transcripts were identified with a more than twofold increase in expression in O4 (+) oligodendrocytes. Many genes required for oligodendrocyte differentiation were upregulated in O4 (+) oligodendrocytes, including numerous genes encoding myelin proteins. Transcriptional changes included genes required for cell adhesion, actin cytoskeleton regulation, and fatty acid and cholesterol biosynthesis. At the O4 (+) stage, there was an increase in expression of a novel proline-rich transmembrane protein (Prmp). Localized to the plasma membrane, Prmp displays adhesive properties that may be important for linking the extracellular matrix to the actin cytoskeleton. Together, our results highlight the usefulness of this discovery-driven experimental strategy to identify genes relevant to oligodendrocyte differentiation and myelination.