C-kit marks late retinal progenitor cells and regulates their differentiation in developing mouse retina

C-kit marks late retinal progenitor cells and regulates their differentiation in developing mouse retina
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DOI:
10.1016/j.ydbio.2006.09.027
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发表时间:
2007-01-01
影响因子:
2.7
通讯作者:
Watanabe, Sumiko
Watanabe, Sumiko
中科院分区:
生物学3区
文献类型:
--
作者:
Koso, Hideto;Satoh, Shinya;Watanabe, Sumiko

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视网膜祖细胞被认为在视网膜发育期间显示改变的增殖和分化,表明视网膜祖细胞群体不是同质的。然而,祖细胞群的组成尚不清楚,部分原因是缺乏识别视网膜祖细胞不同阶段的已知表面标志物。我们发现在视网膜祖细胞的细胞表面抗原c-kit和阶段特异性胚胎抗原-1(SSEA-1)的表达谱在发育过程中发生了显着变化。虽然SSEA-I在发育早期表达,但c-kit表达在晚期祖细胞中达到峰值。这些发育标志物的鉴定使我们能够表征视网膜祖细胞的不同亚群。祖细胞亚群表达SSEA-1,c-kit,或两者都表现出不同的增殖和分化能力。虽然SSEA-1阳性细胞被β-连环蛋白信号增强,但c-kit阳性细胞被Notch信号正向调节。两者合计,我们的数据表明,c-kit和SSEA-I可用于时空区分视网膜祖细胞群体,具有本质上不同的特点。在c-kit配体干细胞因子(SCIF)存在的情况下,逆转录病毒延长c-kit的表达会促进增殖并出现巢蛋白阳性细胞。这表明c-kit,Notch和β-连环蛋白信号网络在视网膜发育中的作用。(c)2006年爱思唯尔公司All rights reserved.
Retinal progenitor cells are believed to display altered proliferation and differentiation during retinal development, suggesting that retinal progenitor cell populations are not homogeneous. However, the composition of progenitor cell populations is not known, due in part to the lack of known surface markers identifying distinct stages of retinal progenitor cells. We found a dramatic change in the expression profile of the cell surface antiaens c-kit and stage-specific embryonic antigen-1 (SSEA-1) in retinal progenitor cells during development. While SSEA-I was expressed early in development, c-kit expression peaked in late stage progenitor cells. The identification of these developmental markers enabled us to characterize distinct sub-populations of retinal progenitor cells. Progenitor cell subpopulations expressing either SSEA-1, c-kit, or both showed different proliferation and differentiation abilities. Although SSEA-1-positive cells were augmented by beta-catenin signaling, c-kit-positive cells were positively regulated by Notch signaling. Taken together, our data suggest that c-kit and SSEA-I can be used to spatiotemporally differentiate retinal progenitor populations that have intrinsically distinct characteristics. Prolonged expression of c-kit by a retrovirus resulted in the promotion of proliferation and the appearance of nestin-positive cells in the presence of the c-kit ligand, stem cell factor (SCIF). This suggests a role for c-kit, Notch, and the beta-catenin signaling network in retinal development. (c) 2006 Elsevier Inc. All rights reserved.