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从成年Chx10(orJ/orJ) 中枢神经视网膜中分离并鉴定神经祖细胞。

Isolation and characterisation of neural progenitor cells from the adult Chx10(orJ/orJ) central neural retina.

作者信息

Kokkinopoulos I, Pearson R A, Macneil A, Dhomen N S, MacLaren R E, Ali R R, Sowden J C

机构信息

Developmental Biology Unit, University College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.

出版信息

Mol Cell Neurosci. 2008 Jul;38(3):359-73. doi: 10.1016/j.mcn.2008.03.008. Epub 2008 Apr 10.

Abstract

Retinal stem cells have been isolated from the ciliary epithelium (CE) of the mammalian retina. However, the central neural retina (CNR) lacks the capability to regenerate, a phenomenon retained by lower vertebrates. Mutations in the Chx10 homeobox gene cause reduced proliferation of retinal progenitor cells during development, leading to microphthalmia. Recently, we showed that in Chx10(orJ/orJ) mice, dividing cells persist in the adult CNR, suggesting the existence of a dormant progenitor population. Here, we show that these cells are proliferative and give rise to neurospheres in vitro, a characteristic of neural stem cells. However, these adult-derived CNR progenitors differ from those of the wildtype CE, leading to de-pigmented, larger and more numerous neurospheres expressing Müller glial cell markers. Our results suggest that lack of Chx10 leads to maintenance of a dormant neural progenitor population in the adult CNR. Furthermore, Chx10 is not required for in vitro proliferation of these progenitors.

摘要

视网膜干细胞已从哺乳动物视网膜的睫状体上皮(CE)中分离出来。然而,中枢神经视网膜(CNR)缺乏再生能力,而低等脊椎动物则保留了这一现象。Chx10同源框基因的突变会导致视网膜祖细胞在发育过程中增殖减少,从而导致小眼症。最近,我们发现,在Chx10(orJ/orJ)小鼠中,成年CNR中存在持续分裂的细胞,这表明存在休眠的祖细胞群体。在此,我们表明这些细胞具有增殖能力,并在体外形成神经球,这是神经干细胞的一个特征。然而,这些源自成年小鼠的CNR祖细胞与野生型CE的祖细胞不同,会产生色素脱失、更大且数量更多的表达穆勒神经胶质细胞标志物的神经球。我们的结果表明,Chx10的缺失导致成年CNR中休眠神经祖细胞群体的维持。此外,这些祖细胞的体外增殖不需要Chx10。

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