Reprogramming retinal pigment epithelium to differentiate toward retinal neurons with Sox2.
Reprogramming retinal pigment epithelium to differentiate toward retinal neurons with Sox2.
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DOI：
10.1002/stem.48
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发表时间：
2009-06
期刊：
影响因子：
5.2
通讯作者：
Wang, Shu-Zhen
中科院分区：
文献类型：
--
作者：
Ma, Wenxin;Yan, Run-Tao;Li, Xiumei;Wang, Shu-Zhen
引导非神经的视网膜色素上皮细胞（RPE）产生视网膜神经元可能为细胞替代提供发育神经元的来源。Sox 2在维持神经祖细胞/干细胞特性和将成纤维细胞转化为多能干细胞中起重要作用。本研究测试了使用Sox 2重编程RPE以在体内和体外向视网膜神经元分化的可能性。Sox 2在鸡视网膜中的表达在祖细胞中、在无长突细胞和神经节细胞层中的离散位置处的细胞中以及在麦氏神经胶质中检测到。Sox 2在发育中的眼睛中的过表达导致RPE的色素沉着减退。在受影响的区域，视网膜神经节细胞标志物的表达在RPE层中变得明显。在RPE细胞培养中，Sox 2促进视网膜神经节和无长突标记物的表达，并抑制与RPE特性相关的基因的表达。使用发育中的视网膜进行的机制研究揭示了Sox 2和bFGF的共表达，bFGF是一种常用于干细胞培养的生长因子，能够在早期发育期间诱导RPE向视网膜转分化（或重编程）。在萎缩性视网膜和损伤性视网膜中观察到Sox 2表达和bFGF表达的类似变化模式。在RPE细胞培养中，Sox 2和bFGF相互增强彼此的表达。Sox 2上调bFGF的表达也发生在视网膜中。这些结果表明，Sox 2可以启动RPE细胞的重编程，向视网膜神经元分化，并可能在此过程中参与bFGF。
Guiding non-neural, retinal pigment epithelium (RPE) to produce retinal neurons may offer a source of developing neurons for cell-replacement. Sox2 plays important roles in maintaining neural progenitor/stem cell properties and in converting fibroblasts into pluripotent stem cells. This study tests the possibility of using Sox2 to reprogram RPE to differentiate towards retinal neurons in vivo and in vitro. Expression of Sox2 in the chick retina was detected in progenitor cells, in cells at a discrete location in the layers of amacrine and ganglion cells, and in Műller glia. Overexpression of Sox2 in the developing eye resulted in hypo-pigmentation of the RPE. In the affected regions, expression of retinal ganglion cell markers became apparent in the RPE layer. In RPE cell culture, Sox2 promoted the expression of retinal ganglion and amacrine markers and suppressed the expression of genes associate with RPE properties. Mechanistic investigation using the developing retina revealed a co-expression of Sox2 and bFGF, a growth factor commonly used in stem cell culture and capable of inducing RPE-to-retina transdifferentiation (or reprogramming) during early development. Similar patterns of changes in Sox2 expression and in bFGF expression were observed in atrophic retina and in injured retina. In RPE cell culture, Sox2 and bFGF mutually enhanced one another's expression. Up-regulation of bFGF expression by Sox2 also occurred in the retina. These results suggest that Sox2 can initiate a reprogramming of RPE cells to differentiate towards retinal neurons and may engage bFGF during the process.
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DOI：
10.1083/jcb.200409182
发表时间：
2005-03-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mansukhani A;Ambrosetti D;Holmes G;Cornivelli L;Basilico C
通讯作者：
Basilico C
影响因子：
2
作者：
BARRINGTON, M;SATTAYASAI, J;EHRLICH, D
通讯作者：
EHRLICH, D
影响因子：
25
作者：
Fischer, AJ;Reh, TA
通讯作者：
Reh, TA
影响因子：
5.3
作者：
Bernardos, Rebecca L.;Barthel, Linda K.;Raymond, Pamela A.
通讯作者：
Raymond, Pamela A.
影响因子：
11.4
作者：
HAN, KY;MANLEY, JL
通讯作者：
MANLEY, JL