最大限度地从成人视网膜干细胞中分化出功能性光感受器。
Maximizing functional photoreceptor differentiation from adult human retinal stem cells.
机构信息
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
出版信息
Stem Cells. 2010 Mar 31;28(3):489-500. doi: 10.1002/stem.279.
Abstract
Retinal stem cells (RSCs) are present in the ciliary margin of the adult human eye and can give rise to all retinal cell types. Here we show that modulation of retinal transcription factor gene expression in human RSCs greatly enriches photoreceptor progeny, and that strong enrichment was obtained with the combined transduction of OTX2 and CRX together with the modulation of CHX10. When these genetically modified human RSC progeny are transplanted into mouse eyes, their retinal integration and differentiation is superior to unmodified RSC progeny. Moreover, electrophysiologic and behavioral tests show that these transplanted cells promote functional recovery in transducin mutant mice. This study suggests that gene modulation in human RSCs may provide a source of photoreceptor cells for the treatment of photoreceptor disease.
摘要
视网膜干细胞（RSCs）存在于成人眼睛的睫状缘，可以产生所有视网膜细胞类型。在这里，我们表明，调节人 RSCs 中的视网膜转录因子基因表达可大大增加光感受器祖细胞的数量，并且通过同时转导 OTX2 和 CRX 并调节 CHX10 可以获得强烈的富集。当将这些经过基因修饰的人 RSC 祖细胞移植到小鼠眼中时，它们的视网膜整合和分化优于未经修饰的 RSC 祖细胞。此外，电生理和行为测试表明，这些移植的细胞可促进转导蛋白突变小鼠的功能恢复。这项研究表明，人 RSCs 中的基因调节可能为治疗光感受器疾病提供光感受器细胞的来源。
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