DNA Methyltransferase Inhibition by RG108 Improves Stemness and Multipotential Differentiation of Human Adipose Tissue-derived Stem Cells.

IF 1.6 4区生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Iranian Journal of Biotechnology Pub Date : 2024-04-01 DOI:10.30498/ijb.2024.435096.3863

Razieh Asgharian, Afrooz Hashemi, Arash Javeri, Masoumeh Fakhr Taha

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引用次数: 0

Abstract

Background: DNA methylation plays important roles in regulating various biological processes, including self-renewal, differentiation and regenerative capacity of stem cells. Previous studies have demonstrated that lineage-specific differentiation of mesenchymal stem cells can be promoted using nontoxic chromatin-modifying drugs.

Objectives: Here we evaluated the impact of RG108, a known DNA methyltransferase inhibitor, on the expression of pluripotency genes in human adipose tissue-derived stem cells (hADSCs) and their proliferation and differentiation.

Materials and methods: Human ADSCs were isolated by collagenase treatment and characterized. Then, ADSCs were treated with 5 µM RG108 for four days. The control and RG108-treated cells were analyzed for the cell cycle progression, apoptosis and the expression of pluripotency genes. Also, ADSCs were cultured in adipogenic and osteogenic differentiation media for three weeks and were assessed by Oil Red O and Alizarin Red S staining and qPCR analysis.

Results: We showed that RG108 treatment increased proliferation of hADSCs and upregulated the expression of pluripotency-related genes. Additionally, RG108 had a positive impact on the differentiation capability of ADSCs. This was evident through elevated levels of Oil Red O staining in the RG108 treatment group. Also, qPCR analysis showed the upregulation of some adipogenic and osteogenic markers by RG108.

Conclusion: These findings indicate that pretreatment with RG108 improves the differentiation potential of ADSCs, probably making these cells more beneficial for cell therapy applications.

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用 RG108 抑制 DNA 甲基转移酶可提高人脂肪组织来源干细胞的干性和多潜能分化。

背景：DNA 甲基化在调节各种生物过程中发挥着重要作用，包括干细胞的自我更新、分化和再生能力。先前的研究表明，使用无毒染色质修饰药物可促进间充质干细胞的系特异性分化：在此，我们评估了已知的DNA甲基转移酶抑制剂RG108对人脂肪组织来源干细胞（hADSCs）多能基因表达及其增殖和分化的影响。然后，用 5 µM RG108 处理 ADSCs 4 天。对对照组和经 RG108 处理的细胞进行细胞周期进展、细胞凋亡和多能基因表达分析。此外，将 ADSCs 在成脂和成骨分化培养基中培养三周，并通过油红 O 和茜素红 S 染色和 qPCR 分析进行评估：结果表明：RG108能增加hADSCs的增殖，并上调多能相关基因的表达。此外，RG108 对 ADSCs 的分化能力也有积极影响。RG108 处理组的油红 O 染色水平升高就证明了这一点。此外，qPCR 分析表明 RG108 上调了一些成脂和成骨标记物：这些研究结果表明，使用 RG108 进行预处理可提高 ADSCs 的分化潜能，从而使这些细胞更有利于细胞疗法的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Iranian Journal of Biotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-

CiteScore

2.60

自引率

7.70%

发文量

期刊介绍： Iranian Journal of Biotechnology (IJB) is published quarterly by the National Institute of Genetic Engineering and Biotechnology. IJB publishes original scientific research papers in the broad area of Biotechnology such as, Agriculture, Animal and Marine Sciences, Basic Sciences, Bioinformatics, Biosafety and Bioethics, Environment, Industry and Mining and Medical Sciences.