Retinal pigment epithelial (RPE) cells are indispensable for eye organogenesis and vision. To realize the therapeutic potential of in vitro-generated RPE cells for cell-replacement therapy of RPE-related retinopathies, molecular mechanisms of RPE specification and maturation need to be investigated. So far, many attempts have been made to decipher the regulatory networks involved in the differentiation of human pluripotent stem cells into RPE cells. Here, we exploited a highly-efficient RPE differentiation protocol to determine global expression patterns of microRNAs (miRNAs) during human embryonic stem cell (hESC) differentiation into RPE using small RNA sequencing. Our results revealed a significant downregulation of pluripotency-associated miRNAs along with a significant upregulation of RPE-associated miRNAs in differentiating cells. Our functional analyses indicated that two RPE-enriched miRNAs (i.e. miR-125b and let-7a) could promote RPE fate at the expense of neural fate during RPE differentiation. Taken together, these mechanistic interrogations might shed light on a better understanding of RPE cell development and provide insights for the future application of these cells in regenerative medicine.

中文翻译：

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MicroRNA分析揭示了人类视网膜色素上皮细胞分化过程中miR-125b和let-7a的重要功能。

视网膜色素上皮（RPE）细胞对于眼睛器官发生和视觉不可或缺。为了实现体外产生的RPE细胞在RPE相关视网膜病变的细胞替代治疗中的治疗潜力，需要研究RPE规格和成熟的分子机制。迄今为止，已经进行了许多尝试来破译与人类多能干细胞向RPE细胞分化有关的调控网络。在这里，我们利用高效的RPE分化方案来确定使用小RNA测序的人类胚胎干细胞（hESC）分化为RPE期间microRNA（miRNA）的整体表达模式。我们的结果显示，分化细胞中多能性相关的miRNA显着下调，RPE相关的miRNA显着上调。我们的功能分析表明，两种富含RPE的miRNA（即miR-125b和let-7a）可以促进RPE的命运，但会损害RPE分化过程中的神经命运。综上所述，这些机制研究可能有助于更好地了解RPE细胞的发育，并为这些细胞在再生医学中的未来应用提供见识。