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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Generation of Rx~+/Pax6~+ neural retinal precursors from embryonic stem cells
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Generation of Rx~+/Pax6~+ neural retinal precursors from embryonic stem cells

机译：从胚胎干细胞生成Rx〜+ / Pax6〜+神经视网膜前体

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摘要

We report directed differentiaion of retinal precursors in vitro from mouse ES cells. Six3~+ rostral brain progenitors are generated by culturing ES cells under serum-free suspension conditions (SFEB culture) in the presence of Wnt and Nodal antagonists (Dkk1 and LeftyA), and subsequently steered to differentiate into Rx~+ cells (16%) by treatment with activin and serum. Consistent with the characteristics of early neural retinal precursors, the induced Rx~+ cells coexpress Pax6 and the mitotic marker Ki67, but not Nestin. The ES cell-derived precursors efficiently generate cells with the photoreceptor phenotype (rhodopsin~+, recoverin~+) when cocultured with embryonic retinal cells. Furthermore, organotypic culture studies demonstrate the selective integration and survival of ES cell-derived cells with the photoreceptor phenotype (marker expression and morphology) in the outer nuclear layer of the retina. Taken together, ES cells treated with SFEB/Dkk1/LeftyA/ serum/activin generate neural retinal precursors, which have the competence of photoreceptor differentiation.
机译：我们报告从小鼠胚胎干细胞体外定向分化的视网膜前体。在Wnt和Nodal拮抗剂（Dkk1和LeftyA）存在下，在无血清悬液条件下（SFEB培养）培养ES细胞，产生了6个3〜+延髓脑祖细胞，随后将其引导分化为Rx〜+细胞（16％）通过激活素和血清治疗。与早期神经视网膜前体的特征一致，诱导的Rx〜+细胞共表达Pax6和有丝分裂标记物Ki67，而不表达Nestin。与胚胎视网膜细胞共培养时，源自ES细胞的前体可有效生成具有感光表型（视紫红质+，恢复蛋白+）的细胞。此外，器官型培养研究表明，在视网膜外核层中具有光感受器表型（标志物表达和形态）的ES细胞衍生细胞的选择性整合和存活。总而言之，用SFEB / Dkk1 / LeftyA /血清/激活素处理的ES细胞产生了神经视网膜前体，它们具有感光细胞分化的能力。

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