Phenotypic and functional heterogeneity of GFAP-expressing cells in vitro: Differential expression of LeX/CD15 by GFAP-expressing multipotent neural stem cells and non-neurogenic astrocytes
Phenotypic and functional heterogeneity of GFAP-expressing cells in vitro: Differential expression of LeX/CD15 by GFAP-expressing multipotent neural stem cells and non-neurogenic astrocytes
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DOI：
10.1002/glia.20281
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发表时间：
2006-02-01
期刊：
影响因子：
6.2
通讯作者：
Sofroniew, MV
中科院分区：
文献类型：
--
作者：
Imura, T;Nakano, I;Sofroniew, MV
最近的研究结果表明，主要的多能神经干细胞（NSC）从出生后和成年小鼠脑分离表达胶质细胞酸性蛋白（GFAP），一种蛋白质通常与星形胶质细胞，和原代星形胶质细胞培养物可以包含GFAP表达细胞作为多能神经干细胞转移到神经原性条件。表达GFAP的神经干细胞与表达GFAP的星形胶质细胞的关系尚不清楚，但具有重要意义。我们比较了来自不同中枢神经系统区域并在不同条件下体外培养的表达GFAP的细胞的表型和神经发生潜能。多重标记免疫组化显示，无论是原代星形胶质细胞培养和贴壁神经源性培养来自出生后或成人脑室周围组织包含GFAP表达细胞的亚群，共表达巢蛋白和LeX/CD 15，两个分子与神经干细胞。与此相反，GFAP表达细胞在类似的培养制备成人大脑皮层没有表达可检测水平的LeX/CD 15，并表现出没有神经原性的潜力。原代星形胶质细胞培养物和贴壁神经源性培养物的LeX/CD 15的活化细胞分选（FACS）显示，能够充当多能神经干细胞的GFAP表达细胞集中在LeX阳性部分中。使用神经球测定和转基因消融策略，我们证实了在原代星形胶质细胞和贴壁神经源性培养物中主要的NSG是表达GFA-P的细胞。这些研究结果表明，GFAP表达细胞来自出生后和成人前脑是异质性的分子表型和神经原性的潜力在体外，这种异质性存在之前暴露于神经原性条件。这些发现提供了证据表明，GFAP表达的神经干细胞的表型和功能不同于非神经源性星形胶质细胞。(C)2005 Wiley-Liss，Inc.
Recent findings show that the predominant multipotent neural stem cells (NSCs) isolated from postnatal and adult mouse brain express glial fibrillary acid protein (GFAP), a protein commonly associated with astrocytes, and that primary astrocyte cultures can contain GFAP-expressing cells that act as multipotent NSCs when transferred to neurogenic conditions. The relationship of GFAP-expressing NSCs to GFAP-expressing astrocytes is unclear, but has important implications. We compared the phenotype and neurogenic potential of GFAP-expressing cells derived from different CNS regions and maintained in vitro under different conditions. Multiple labeling immunohistochemistry revealed that both primary astrocyte cultures and adherent neurogenic cultures derived from postnatal or adult periventricular tissue contained subpopulations of GFAP-expressing cells that co-expressed nestin and LeX/CD15, two molecules associated with NSCs. In contrast, GFAP-expressing cells in similar cultures prepared from adult cerebral cortex did not express detectable levels of LeX/CD15, and exhibited no neurogenic potential. Fluorescence-activated cell sorting (FACS) of both primary astrocyte cultures and adherent neurogenic cultures for LeX/CD15 showed that GFAP-expressing cells competent to act as multipotent NSCs were concentrated in the LeX-positive fraction. Using neurosphere assays and a transgenic ablation strategy, we confirmed that the predominant NSGs in primary astrocyte and adherent neurogenic cultures were GFA-P-expressing cells. These findings demonstrate that GFAP-expressing cells derived from postnatal and adult forebrain are heterogeneous in both molecular phenotype and neurogenic potential in vitro, and that this heterogeneity exists before exposure to neurogenic conditions. The findings provide evidence that GFAP-expressing NSCs are phenotypically and functionally distinct from non-neurogenic astrocytes. (C) 2005 Wiley-Liss, Inc.