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与人类胚胎干细胞分化为人类视网膜神经节细胞相关的微小RNA变化

miRNA changes associated with differentiation of human embryonic stem cells into human retinal ganglion cells.

作者信息

Esmaeili Maryam, Smith Daniel A, Mead Ben

机构信息

School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF24 4HQ, UK.

Wales Kidney Research Unit, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.

出版信息

Sci Rep. 2024 Dec 30;14(1):31895. doi: 10.1038/s41598-024-83381-9.

Abstract

miRNA, short non-coding RNA, are rapidly emerging as important regulators in cell homeostasis, as well as potential players in cellular degeneration. The latter has led to interest in them as both biomarkers and as potential therapeutics. Retinal ganglion cells (RGC), whose axons connect the eye to the brain, are central nervous system cells of great interest, yet their study is largely restricted to animals due to the difficulty in obtaining healthy human RGC. Using a CRISPR/Cas9-based reporter embryonic stem cell line, human RGC were generated and their miRNA profile characterized using NanoString miRNA assays. We identified a variety of retinal specific miRNA upregulated in ESC-derived RGC, with half of the most abundant miRNA also detectable in purified rat RGC. Several miRNA were however identified to be unique to RGC from human. The findings show which miRNA are abundant in RGC and the limited congruence with animal derived RGC. These data could be used to understand miRNA's role in RGC function, as well as potential biomarkers or therapies in retinal diseases involving RGC degeneration.

摘要

微小RNA(miRNA)是短链非编码RNA,正迅速成为细胞稳态的重要调节因子,也是细胞退化过程中的潜在参与者。后者引发了人们对其作为生物标志物和潜在治疗手段的兴趣。视网膜神经节细胞(RGC)的轴突将眼睛与大脑相连,是备受关注的中枢神经系统细胞,但由于难以获得健康的人类RGC,对它们的研究主要局限于动物。利用基于CRISPR/Cas9的报告胚胎干细胞系,生成了人类RGC,并使用NanoString miRNA检测方法对其miRNA谱进行了表征。我们鉴定出多种在胚胎干细胞衍生的RGC中上调的视网膜特异性miRNA,其中一半最丰富的miRNA在纯化的大鼠RGC中也可检测到。然而,有几种miRNA被确定为人类RGC所特有。这些发现表明了哪些miRNA在RGC中丰富,以及与动物来源的RGC的有限一致性。这些数据可用于了解miRNA在RGC功能中的作用,以及在涉及RGC退化的视网膜疾病中的潜在生物标志物或治疗方法。

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