MicroRNA Profile of Human Bone Marrow Mesenchymal Stem Cells during Hepatic Differentiation and Therapy.
MicroRNA Profile of Human Bone Marrow Mesenchymal Stem Cells during Hepatic Differentiation and Therapy.
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人骨髓间充质干细胞在肝分化和治疗过程中的 MicroRNA 谱
DOI：
10.7150/ijms.67639
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发表时间：
2022
影响因子：
3.6
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Jiang J;Xin J;Ding W;Shi D;Sun S;Guo B;Zhou X;Zheng C;Li J
背景和目标：microRNAs（miRNAs）在人骨髓间充质干细胞（hBMSCs）向肝细胞分化及体内治疗应用中发挥重要作用。然而，miRNA调控的机制仍然未知。本研究的目的是分析miRNA在改善hBMSC-Heps功能中的作用。研究方法：通过转录组测序鉴定hBMSC-Heps的特征性miRNA，并通过定量实时聚合酶链反应（qRT-PCR）验证。使用体内hBMSC移植模型来评估在患有暴发性肝功能衰竭（FHF）的猪中hBMSC治疗期间miRNA对肝再生的调节作用。通过转染miRNA激活剂或抑制剂到hBMSCs中，在肝细胞分化过程中证实了重要miRNA分子的生物学功能。结果：hBMSC-Heps的转录组具有与未分化hBMSCs不同的特征。hBMSC诱导分化后第10天和第20天，共检测到77个与肝细胞功能直接相关的miRNAs。在前10个显著差异表达和前10个最丰富的miRNA中，选择了9个表现出逐渐变化模式的miRNA用于进一步分析。通过体外qRT-PCR证实了9种miRNAs的表达，并在猪hBMSC移植模型中显示出相同的体内变化趋势。这些miRNAs的功能实验表明，hsa-miR-26 b-5 p和hsa-miR-148 a-3 p的激活剂和hsa-miR-423- 3 p的抑制剂足以促进hBMSC分化为肝细胞样细胞。结论：miRNA的转录组表达谱揭示了hBMSC-Heps分化发育的基础。三种miRNAs（hsa-miR-26 b-5 p、hsa-miR-148 a-3 p和hsa-miR-423- 3 p）的操作显著改善了肝细胞生成和肝再生，表明这些miRNAs具有未来临床应用的潜力。
Background and Aims: MicroRNAs (miRNAs) play important roles in hepatocyte differentiation from human bone marrow mesenchymal stem cells (hBMSCs) and the therapeutic application in vivo. However, the mechanisms of miRNA regulation are still unknown. This study aimed to profile the miRNA basis for improving the function of hBMSC-differentiated hepatocyte-like cells (hBMSC-Heps). Methods: Characteristic miRNAs of hBMSC-Heps were identified by transcriptome sequencing and validated by quantitative real-time polymerase chain reaction (qRT-PCR). An in vivo hBMSC transplantation model was used to assess the regulatory effects of miRNAs on liver regeneration during hBMSC therapy in pigs with fulminant hepatic failure (FHF). The biological functions of significant miRNA molecules were confirmed by transfection of miRNA activators or inhibitors into hBMSCs during hepatogenic differentiation. Results: The transcriptome of hBMSC-Heps showed characteristics distinct from those of undifferentiated hBMSCs. A total of 77 miRNAs were significantly differentially expressed in hBMSC-Heps at day 10 and day 20 after hBMSC differentiation that were directly related to the functions of hepatocytes. Among the top 10 significantly differentially expressed and the top 10 most abundant miRNAs, nine miRNAs that exhibited a pattern of gradual change were chosen for further analysis. The expression of nine miRNAs was confirmed by qRT-PCR in vitro and showed the same changing trends in vivo in an hBMSC transplantation model in pigs. Functional experiments with these miRNAs showed that activators of hsa-miR-26b-5p and hsa-miR-148a-3p and an inhibitor of hsa-miR-423-3p were sufficient to improve the differentiation of hBMSCs into hepatocyte-like cells. Conclusions: Transcriptome profiles of miRNA revealed the basis of the differentiation and development of hBMSC-Heps. Manipulation of three miRNAs (hsa-miR-26b-5p, hsa-miR-148a-3p and hsa-miR-423-3p) significantly improved hepatocyte generation and liver regeneration, indicating the potential of these miRNAs for future clinical applications.
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影响因子：
3.6
作者：
Li J;Xin J;Zhang L;Wu J;Jiang L;Zhou Q;Li J;Guo J;Cao H;Li L
通讯作者：
Li L
影响因子：
4
作者：
Doddapaneni, Ravi .;Chawla, Yogesh K.;Chakraborti, Anuradha
通讯作者：
Chakraborti, Anuradha
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J
乙型肝炎相关慢加急性肝衰竭中外周血单核细胞 microRNA 的特征
影响因子：
4.6
作者：
Ding W;Xin J;Jiang L;Zhou Q;Wu T;Shi D;Lin B;Li L;Li J
通讯作者：
Li J
影响因子：
13.5
作者：
Rogler, Charles E.;LeVoci, Lauretta;Rogler, Leslie E.
通讯作者：
Rogler, Leslie E.