Kokkinopoulos I, Pearson R A, Macneil A, Dhomen N S, MacLaren R E, Ali R R, Sowden J C
Developmental Biology Unit, University College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
Mol Cell Neurosci. 2008 Jul;38(3):359-73. doi: 10.1016/j.mcn.2008.03.008. Epub 2008 Apr 10.
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.
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。
