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微小 RNA 可有效诱导间充质干细胞形成胰岛素产生细胞。

MicroRNAs can effectively induce formation of insulin-producing cells from mesenchymal stem cells.

机构信息

Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

出版信息

J Tissue Eng Regen Med. 2017 Dec;11(12):3457-3468. doi: 10.1002/term.2259. Epub 2017 Apr 10.

Abstract

MicroRNAs regulate insulin secretion, pancreatic development and beta cell differentiation. However, the function of microRNAs in the formation of insulin-producing cells (IPCs) from adult stem cells is poorly understood. We examine the microRNA expression profile in nestin-positive umbilical cord-derived mesenchymal stem cells (N-UCMSCs) and nestin-positive pancreatic mesenchymal stem cells using a deep sequencing approach. We also selected specific microRNAs for overexpression in N-UCMSCs and found that miR-375 and miR-26a induced IPCs differentiation from N-UCMSCs by downregulating target genes including mtpn, sox6, bhlhe22 and ccnd1. Small interfering RNAs were also used to knock down these genes in N-UCMSCs to induce the formation of IPCs. These results suggest that endogenous microRNAs involved in the formation of IPCs from adult stem cells show promise for advancing the development of an effective cell transplant therapy for diabetes. Copyright © 2017 John Wiley & Sons, Ltd.

摘要

微小 RNA 调节胰岛素分泌、胰腺发育和β细胞分化。然而,微小 RNA 在成年干细胞形成胰岛素分泌细胞(IPC)中的作用还知之甚少。我们使用深度测序方法检查了巢蛋白阳性脐带间充质干细胞(N-UCMSCs)和巢蛋白阳性胰腺间充质干细胞中的微小 RNA 表达谱。我们还选择了特定的微小 RNA 在 N-UCMSCs 中过表达,并发现 miR-375 和 miR-26a 通过下调包括 mtpn、sox6、bhlhe22 和 ccnd1 在内的靶基因,诱导 N-UCMSCs 向 IPC 分化。还使用小干扰 RNA 敲低 N-UCMSCs 中的这些基因,诱导 IPC 的形成。这些结果表明,参与成年干细胞形成 IPC 的内源性微小 RNA 为开发有效的糖尿病细胞移植治疗方法提供了希望。版权所有©2017 约翰威立父子公司

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