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miR-7 Modulates hESC Differentiation into Insulin-Producing Beta-like Cells and Contributes to Cell Maturation.
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2018-06-15 , DOI: 10.1016/j.omtn.2018.06.002
Javier López-Beas 1 , Vivian Capilla-González 1 , Yolanda Aguilera 1 , Nuria Mellado 1 , Christian C Lachaud 1 , Franz Martín 2 , Tarik Smani 3 , Bernat Soria 2 , Abdelkrim Hmadcha 2
Affiliation  

Human pluripotent stem cells retain the extraordinary capacity to differentiate into pancreatic beta cells. For this particular lineage, more effort is still required to stress the importance of developing an efficient, reproducible, easy, and cost-effective differentiation protocol to obtain more mature, homogeneous, and functional insulin-secreting cells. In addition, microRNAs (miRNAs) have emerged as a class of small non-coding RNAs that regulate many cellular processes, including pancreatic differentiation. Some miRNAs are known to be preferentially expressed in islets. Of note, miR-375 and miR-7 are two of the most abundant pancreatic miRNAs, and they are necessary for proper pancreatic islet development. Here we provide new insight into specific miRNAs involved in pancreatic differentiation. We found that miR-7 is differentially expressed during the differentiation of human embryonic stem cells (hESCs) into a beta cell-like phenotype and that its modulation plays an important role in generating mature pancreatic beta cells. This strategy may be exploited to optimize the potential for in vitro differentiation of hESCs into insulin-producing beta-like cells for use in preclinical studies and future clinical applications as well as the prospective uses of miRNAs to improve this process.



中文翻译:

miR-7调节hESC分化为产生胰岛素的β样细胞,并有助于细胞成熟。

人多能干细胞保留了分化为胰腺β细胞的非凡能力。对于此特定谱系,仍需要付出更多的努力来强调开发有效,可重现,简便且具有成本效益的分化方案以获得更成熟,均一且功能性的胰岛素分泌细胞的重要性。此外,microRNA(miRNA)已作为一类小的非编码RNA出现,它们调节许多细胞过程,包括胰腺分化。已知一些miRNA在胰岛中优先表达。值得注意的是,miR-375和miR-7是最丰富的胰腺miRNA中的两个,它们对于正常胰岛发育是必需的。在这里,我们提供了涉及胰腺分化的特定miRNA的新见解。我们发现,在人类胚胎干细胞(hESCs)分化为β细胞样表型的过程中,miR-7差异表达,并且它的调节在生成成熟的胰腺β细胞中起着重要的作用。可以利用该策略来优化潜在的hESCs在体外分化为产生胰岛素的β样细胞,用于临床前研究和未来的临床应用以及miRNA改善这一过程的前瞻性用途。

更新日期:2018-06-15
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