A novel tsRNA-16902 regulating the adipogenic differentiation of human bone marrow mesenchymal stem cells
A novel tsRNA-16902 regulating the adipogenic differentiation of human bone marrow mesenchymal stem cells
复制标题
新型tsRNA-16902调节人骨髓间充质干细胞的成脂分化
DOI：
10.1186/s13287-020-01882-6
复制
发表时间：
2020-08-24
影响因子：
7.5
通讯作者：
Li, Weidong
中科院分区：
文献类型：
--
作者：
Wang, Tao;Mei, Jun;Li, Weidong
背景：转移RNA衍生的小RNA（TSRNA）是最近发现的非编码RNA的形式，能够调节多种生理过程。然而，TSRNA在HMSC掺杂分化中的作用仍然尚不完全理解。 The purpose of this study was to identify the novel tsRNA-16902 as a regulator of hMSC adipogenic differentiation.Methods: In this study, we conducted transcriptomic sequencing of hMSCs after inducing their adipogenic differentiation, and we were thereby able to clarify the molecular mechanism underlying the role of tsRNA-16902 in this context via a series of molecular biology方法：results：当我们击倒tsRNA-16902表达时，这种损害的HMSC成型分化和相关的标记基因表达。生物信息学分析进一步揭示了针对视黄酸受体伽马（RAR GAMMA）的TSRNA-16902。荧光素酶报告基因测定也证实了TSRNA-16902与RAR GAMMA 3'非翻译区域结合的能力。与此相一致，RARγ的过表达导致HMSC脂肪形成受损。进一步的分析表明，在过表达的RAR伽马或TSRNA-16902被击倒的细胞中，SMAD2/3磷酸化增加了。我们还评估了HMSC的脂肪生成分化，其中TSRNA-16902被击倒，同时添加了SMAD2/3抑制剂以破坏SMAD2/3磷酸化。在添加SMAD2/3信号抑制剂相对于TSRNA-16902单独敲低时，添加Smad2/3信号抑制剂后，将TsRNA-16902被击倒的HMSC的成型分化进一步增强。结论：通过对TSRNA的全面分析TSRNA的全面分析，这些分析在HMSC Adip Adip Adips Nictiate中差异化，以前是差异化的。脂肪形成的未表征调节剂。 TSRNA-16902能够通过SMAD2/3信号通路靶向RAR伽马来调节HMSC脂肪生成分化。因此，我们的结果可能会强调治疗肥胖症的新颖价值策略。
BackgroundTransfer RNA-derived small RNAs (tsRNAs) are a recently discovered form of non-coding RNA capable of regulating myriad physiological processes. The role of tsRNAs in hMSC adipogenic differentiation, however, remains incompletely understood. The purpose of this study was to identify the novel tsRNA-16902 as a regulator of hMSC adipogenic differentiation.MethodsIn this study, we conducted transcriptomic sequencing of hMSCs after inducing their adipogenic differentiation, and we were thereby able to clarify the molecular mechanism underlying the role of tsRNA-16902 in this context via a series of molecular biology methods.ResultsWhen we knocked down tsRNA-16902 expression, this impaired hMSC adipogenic differentiation and associated marker gene expression. Bioinformatics analyses further revealed tsRNA-16902 to target retinoic acid receptor γ (RARγ). Luciferase reporter assays also confirmed the ability of tsRNA-16902 to bind to the RARγ 3′-untranslated region. Consistent with this, RARγ overexpression led to impaired hMSC adipogenesis. Further analyses revealed that Smad2/3 phosphorylation was increased in cells that either overexpressed RARγ or in which tsRNA-16902 had been knocked down. We also assessed the adipogenic differentiation of hMSCs in which tsRNA-16902 was knocked down and at the same time a Smad2/3 inhibitor was added to disrupt Smad2/3 phosphorylation. The adipogenic differentiation of hMSCs in which tsRNA-16902 was knocked down was further enhanced upon the addition of a Smad2/3 signaling inhibitor relative to tsRNA-16902 knockdown alone.ConclusionsThrough a comprehensive profiling analysis of tsRNAs that were differentially expressed in the context of hMSC adipogenic differentiation, we were able to identify tsRNA-16902 as a previously uncharacterized regulator of adipogenesis. tsRNA-16902 is able to regulate hMSC adipogenic differentiation by targeting RARγ via the Smad2/3 signaling pathway. Together, our results may thus highlight novel strategies of value for treating obesity.