MicroRNAs (miRNAs) that play key roles in the generation of insulin-producing cells from stem cells provide a cell-based approach for insulin replacement therapy. In this study, we used next-generation sequencing to detect the miRNA expression profile of normal mouse pancreatic β cells, non-β cells, bone marrow mesenchymal stem cells (BM-MSCs), and adipose-derived stem cells (ADSCs) and determined relative miRNA expression levels in mouse pancreatic β cells. After the novel mouse miRNA candidates were identified using miRDeep 2.0, we found that Chr13_novelMiR7354-5p, a novel miRNA candidate, significantly promoted the differentiation of BM-MSCs into insulin-producing cells . Furthermore, Chr13_novelMiR7354-5p-transfected BM-MSCs reversed hyperglycemia in streptozotocin (STZ)-treated diabetic mice. In addition, bioinformatics analyses, a luciferase reporter assay, and western blotting demonstrated that Chr13_novelMiR7354-5p targeted Notch1 and Rbpj. Our results provide compelling evidence of the existence of 65 novel mouse miRNA candidates and present a new treatment strategy to generate insulin-producing cells from stem cells.

中文翻译：

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新型小鼠 miRNA Chr13_novelMiR7354-5p 促进骨髓间充质干细胞分化为胰岛素生成细胞


MicroRNA (miRNA) 在干细胞产生胰岛素细胞的过程中发挥着关键作用，为胰岛素替代疗法提供了一种基于细胞的方法。在本研究中，我们利用二代测序技术检测正常小鼠胰腺β细胞、非β细胞、骨髓间充质干细胞（BM-MSCs）和脂肪源性干细胞（ADSCs）的miRNA表达谱，并确定小鼠胰腺β细胞中相对miRNA表达水平。使用 miRDeep 2.0 鉴定出新的小鼠 miRNA 候选者后，我们发现新的 miRNA 候选者 Chr13_novelMiR7354-5p 显着促进 BM-MSC 向胰岛素产生细胞的分化。此外，Chr13_novelMiR7354-5p 转染的 BM-MSC 逆转了链脲佐菌素 (STZ) 治疗的糖尿病小鼠的高血糖症。此外，生物信息学分析、荧光素酶报告基因测定和蛋白质印迹表明 Chr13_novelMiR7354-5p 靶向 Notch1 和 Rbpj。我们的结果提供了令人信服的证据，证明 65 种新型小鼠 miRNA 候选物的存在，并提出了一种从干细胞产生胰岛素产生细胞的新治疗策略。