CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells

CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells
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DOI:
10.1158/0008-5472.can-07-0183
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发表时间:
2007-06-15
期刊:
影响因子:
11.2
通讯作者:
Nuber, Ulrike A.
Nuber, Ulrike A.
中科院分区:
医学1区
文献类型:
--
作者:
Pfenninger, Cosima V.;Roschupkina, Teona;Nuber, Ulrike A.

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已经使用针对表面蛋白CD 133的抗体富集了人脑肿瘤干细胞。识别CD 133的抗体也用于从胎儿人脑中分离正常神经干细胞,这表明正常神经干细胞和脑肿瘤干细胞之间可能存在谱系关系。CD 133阳性的脑肿瘤干细胞是否可以来自于CD 133阳性的神经干细胞或祖细胞仍然需要直接的实验证据,而对这样的调查的重要一步是正常的CD 133呈递细胞的胚胎和成人大脑的神经源性区域的识别和表征。在这里,我们提出的证据表明,CD 133是胚胎神经干细胞,中间放射状胶质细胞/室管膜细胞类型在出生后的早期阶段,室管膜细胞在成人大脑中的标记,但不是在成人脑室下区的神经源性星形胶质细胞。我们的研究结果表明,脑肿瘤干细胞的起源有两种主要的可能性:一个衍生自CD 133表达细胞,这是通常不存在于成人大脑(胚胎神经干细胞和出生后早期中间放射状胶质细胞/室管膜细胞类型),或从CD 133阳性室管膜细胞在成人大脑,这是,然而,通常被认为是有丝分裂后。或者,脑肿瘤干细胞可以来源于成人脑中增殖但CD 133阴性的神经源性星形胶质细胞。在后一种情况下,脑肿瘤的发展将涉及CD 133的产生。
Human brain tumor stem cells have been enriched using antibodies against the surface protein CD133. An antibody recognizing CD133 also served to isolate normal neural stem cells from fetal human brain, suggesting a possible lineage relationship between normal neural and brain tumor stem cells. Whether CD133-positive brain tumor stem cells can be derived from CD133-positive neural stem or progenitor cells still requires direct experimental evidence, and an important step toward such investigations is the identification and characterization of normal CD133-presenting cells in neurogenic regions of the embryonic and adult brain. Here, we present evidence that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in the adult subventricular zone. Our findings suggest two principal possibilities for the origin of brain tumor stem cells: a derivation from CD133-expressing cells, which are normally not present in the adult brain (embryonic neural stem cells and an early postnatal intermediate radial glial/ependymal cell type), or from CD133-positive ependymal cells in the adult brain, which are, however, generally regarded as postmitotic. Alternatively, brain tumor stem cells could be derived from proliferative but CD133-negative neurogenic astrocytes in the adult brain. In the latter case, brain tumor development would involve the production of CD133.