PDGFRα Expression Distinguishes GFAP-Expressing Neural Stem Cells from PDGF-Responsive Neural Precursors in the Adult Periventricular Area

PDGFRα Expression Distinguishes GFAP-Expressing Neural Stem Cells from PDGF-Responsive Neural Precursors in the Adult Periventricular Area
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DOI:
10.1523/jneurosci.1531-11.2011
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发表时间:
2011-06-29
影响因子:
5.3
通讯作者:
Weiss, Samuel
Weiss, Samuel
中科院分区:
医学1区
文献类型:
--
作者:
Chojnacki, Andrew;Mak, Gloria;Weiss, Samuel

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杰克逊等人。 (2006) 报道,表达成人胶质纤维酸性蛋白 (GFAP) 的神经干细胞 (NSC) 也表达血小板源性生长因子 (PDGF) 受体-α (PDGFR α),并且 PDGF 的刺激诱导了神经胶质瘤样肿块的形成。在这里,我们重新检查了成人脑室周围区域三维组织内 PDGFR α 和 GFAP 表达之间的关系。使用四种独立的 PDGFR α 抗体,我们发现成年小鼠表达 GFAP 的 NSC 和表达 PDGFR α 的细胞代表两个不同的神经前体群体。对在 PDGFR α 启动子控制下表达核定位增强绿色荧光蛋白的小鼠系的成年脑室周围区域进行检查,证实表达 GFAP 的 NSC 不表达 PDGFR α。此外,发现PDGF反应性神经前体细胞至少有一层位于室管膜层下方,并且均匀分布在侧心室壁上,这与报道的表达GFAP的成体NSC的斑片状且通常位于室管膜上的定位形成鲜明对比。成人表达 PDGFR α 的神经前体细胞也被发现不表达 GFAP。 PDGF 反应性神经前体细胞(而非表达 GFAP 的 NSC)对 PDGF 的输注作出反应,产生神经胶质瘤样肿块。我们的结果不支持以下观点:表达 GFAP 的 NSC 是脑室内输注 PDGF 后形成的神经胶质瘤样肿块的起源。
Jackson et al. (2006) have reported that adult glial fibrillary acid protein (GFAP)-expressing neural stem cells (NSCs) also express platelet-derived growth factor (PDGF) receptor-alpha (PDGFR alpha), and that their stimulation by PDGF induced the formation of a glioma-like mass. Here, we reexamined the relationship between PDGFR alpha and GFAP expression within the three-dimensional organization of the adult periventricular area. Using four independent PDGFR alpha antibodies, we found that adult mouse GFAP-expressing NSCs and PDGFR alpha-expressing cells represent two distinct populations of neural precursors. Examination of the adult periventricular area in a mouse line that expresses nuclear-localized enhanced green fluorescent protein under the control of the PDGFR alpha promoter confirmed that GFAP-expressing NSCs do not express PDGFR alpha. Furthermore, PDGF-responsive neural precursors were found at least one cell layer subjacent to the ependymal layer, and were evenly distributed across the lateral ventricular wall, which contrasts with the reported patchy and often ependymal localization of adult GFAP-expressing NSCs. Adult human PDGFR alpha-expressing neural precursors were also found not to express GFAP. PDGF-responsive neural precursors, but not GFAP-expressing NSCs, responded to infusions of PDGF by generating glioma-like masses. Our results do not support the view that GFAP-expressing NSCs are the origin of glioma-like masses that form after intraventricular PDGF infusion.