Novel Mouse miRNA Chr13_novelMiR7354-5p Improves Bone-Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells
Novel Mouse miRNA Chr13_novelMiR7354-5p Improves Bone-Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells
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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
DOI：
10.1016/j.omtn.2020.01.001
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Xining Pang
中科院分区：
文献类型：
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作者：
Feng Zhao;Xiaoyu Liu;Zhe Wang;Hongxin Lang;Tao Zhang;Rui Wang;Xuewen Lin;Dan He;Ping Shi;Xining Pang
在从干细胞产生胰岛素产生细胞中起关键作用的微小RNA（miRNAs）为胰岛素替代疗法提供了基于细胞的方法。本研究采用新一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）和脂肪干细胞（ADSCs）的miRNA表达谱，并确定小鼠胰腺β细胞中miRNA的相对表达水平。使用miRDeep 2.0鉴定新型小鼠miRNA候选物后，我们发现新型miRNA候选物Chr13_novelMiR7354- 5 p在体外显着促进BM-MSC分化为胰岛素产生细胞。此外，Chr13_novelMiR7354- 5 p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证明Chr13_novelMiR7354- 5 p靶向Notch 1和Rbpj。我们的研究结果提供了令人信服的证据，证明存在65种新的小鼠miRNA候选物，并提出了一种新的治疗策略，从干细胞中产生胰岛素产生细胞。
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 cellsin vitro. 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.