The miRNA profile of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis.
The miRNA profile of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis.
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DOI：
10.1371/journal.pone.0055272
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
McCarthy MI
中科院分区：
文献类型：
--
作者：
van de Bunt M;Gaulton KJ;Parts L;Moran I;Johnson PR;Lindgren CM;Ferrer J;Gloyn AL;McCarthy MI
近年来，对2型糖尿病(T2D)易感性遗传学的研究进展集中于对胰岛β细胞内转录活性的调节。MicroRNAs(MiRNAs)是调节控制的重要组成部分，在人类疾病的发展和血糖稳态的控制中具有已被证明的作用。我们开始建立人胰岛和丰富的β细胞群体的miRNA图谱，并探索它们与T2D易感性的潜在关系。我们使用Illumina小RNA测序技术对三种制剂中的miRNA组分进行了分析，每种制剂都是原代人类胰岛和通过荧光激活细胞分选产生的浓缩的β细胞。总共发现366个miRNAs在胰岛中表达(即100次累计读取)，346个在β细胞中表达；在总共384个独特的miRNAs中，328个是共享的。将胰岛细胞miRNA图谱与其他15个人类组织的miRNA图谱进行比较，发现40个miRNA在胰岛中主要表达(即占所有组织读数的50%)。一些高表达的胰岛miRNAs，如miR-375，已经确定了在胰岛功能调节中的作用，但其他的(例如miR-27b-3p，miR-192-5p)以前没有在胰岛生物学的背景下被描述。作为探索胰岛表达的miRNAs及其预测的mRNA靶点在T2D发病机制中作用的第一步，我们查看了这些位置上已发表的T2D关联信号。我们发现有证据表明，预测的胰岛表达的miRNAs的mRNA靶标被T2D关联信号整体富含(p值和lt；0.01，q值和lt；0.1)。在6个具有全基因组T2D关联证据的基因座(AP3S2、KCNK16、NOTCH2、SCL30A8、VPS26A和WFS1)上，预测了胰岛表达的miRNAs的mRNA靶点重叠的潜在因果变体。总之，我们描述了人类胰岛和β细胞的miRNA图谱，并提供了将胰岛miRNAs与T2D发病联系起来的证据。
Recent advances in the understanding of the genetics of type 2 diabetes (T2D) susceptibility have focused attention on the regulation of transcriptional activity within the pancreatic beta-cell. MicroRNAs (miRNAs) represent an important component of regulatory control, and have proven roles in the development of human disease and control of glucose homeostasis. We set out to establish the miRNA profile of human pancreatic islets and of enriched beta-cell populations, and to explore their potential involvement in T2D susceptibility. We used Illumina small RNA sequencing to profile the miRNA fraction in three preparations each of primary human islets and of enriched beta-cells generated by fluorescence-activated cell sorting. In total, 366 miRNAs were found to be expressed (i.e. >100 cumulative reads) in islets and 346 in beta-cells; of the total of 384 unique miRNAs, 328 were shared. A comparison of the islet-cell miRNA profile with those of 15 other human tissues identified 40 miRNAs predominantly expressed (i.e. >50% of all reads seen across the tissues) in islets. Several highly-expressed islet miRNAs, such as miR-375, have established roles in the regulation of islet function, but others (e.g. miR-27b-3p, miR-192-5p) have not previously been described in the context of islet biology. As a first step towards exploring the role of islet-expressed miRNAs and their predicted mRNA targets in T2D pathogenesis, we looked at published T2D association signals across these sites. We found evidence that predicted mRNA targets of islet-expressed miRNAs were globally enriched for signals of T2D association (p-values <0.01, q-values <0.1). At six loci with genome-wide evidence for T2D association (AP3S2, KCNK16, NOTCH2, SCL30A8, VPS26A, and WFS1) predicted mRNA target sites for islet-expressed miRNAs overlapped potentially causal variants. In conclusion, we have described the miRNA profile of human islets and beta-cells and provide evidence linking islet miRNAs to T2D pathogenesis.
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影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
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通讯作者：
Seielstad, Mark
影响因子：
3.5
作者：
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通讯作者：
Bowcock, Anne M.
影响因子：
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作者：
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通讯作者：
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