Lidi Deng, Siqi Yi, Xiaohui Yin, Yang Li, Qingxian Luan
{"title":"下调MFN2通过PI3K/Akt/GSK-3β/Wnt信号通路促进诱导多能干细胞向间充质干细胞的分化。","authors":"Lidi Deng, Siqi Yi, Xiaohui Yin, Yang Li, Qingxian Luan","doi":"10.1089/scd.2021.0316","DOIUrl":null,"url":null,"abstract":"<p><p>Understanding the mechanism of the differentiation of induced pluripotent stem cells (iPSCs) into mesenchymal stem cells (MSCs) and promoting the production efficiency of iPSC-derived MSCs (iPSC-MSCs) are critical to periodontal tissue engineering. However, the gene networks that control this differentiation process from iPSCs into MSCs are poorly understood. We demonstrated that <i>MFN2</i> knockdown showed a positive effect on the triploblastic and MSC differentiation from iPSCs. Activation of the PI3K/Akt signaling pathway by <i>MFN2</i> knockdown activated the Wnt/β-catenin signaling pathway by inhibiting GSK-3β and reducing β-catenin degradation. Inhibitor of the PI3K/Akt signaling pathway normalized the enhanced efficiency of differentiation into MSCs of <i>MFN2</i>-KD iPSCs and Wnt activator-treated control iPSCs. <i>MFN2</i>-OE iPSCs displayed an opposite phenotype. In conclusion, downregulating <i>MFN2</i> promotes the differentiation of iPSCs into MSCs by activating the PI3K/Akt/GSK-3β/Wnt signaling pathway. Our results reveal a crucial function and mechanism for <i>MFN2</i> in regulating MSC differentiation from iPSCs, which will provide new ideas for periodontal tissue engineering and periodontal regenerative treatment by using iPSC-MSCs.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 7-8","pages":"181-194"},"PeriodicalIF":2.5000,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Downregulating <i>MFN2</i> Promotes the Differentiation of Induced Pluripotent Stem Cells into Mesenchymal Stem Cells through the PI3K/Akt/GSK-3β/Wnt Signaling Pathway.\",\"authors\":\"Lidi Deng, Siqi Yi, Xiaohui Yin, Yang Li, Qingxian Luan\",\"doi\":\"10.1089/scd.2021.0316\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Understanding the mechanism of the differentiation of induced pluripotent stem cells (iPSCs) into mesenchymal stem cells (MSCs) and promoting the production efficiency of iPSC-derived MSCs (iPSC-MSCs) are critical to periodontal tissue engineering. However, the gene networks that control this differentiation process from iPSCs into MSCs are poorly understood. We demonstrated that <i>MFN2</i> knockdown showed a positive effect on the triploblastic and MSC differentiation from iPSCs. Activation of the PI3K/Akt signaling pathway by <i>MFN2</i> knockdown activated the Wnt/β-catenin signaling pathway by inhibiting GSK-3β and reducing β-catenin degradation. Inhibitor of the PI3K/Akt signaling pathway normalized the enhanced efficiency of differentiation into MSCs of <i>MFN2</i>-KD iPSCs and Wnt activator-treated control iPSCs. <i>MFN2</i>-OE iPSCs displayed an opposite phenotype. In conclusion, downregulating <i>MFN2</i> promotes the differentiation of iPSCs into MSCs by activating the PI3K/Akt/GSK-3β/Wnt signaling pathway. Our results reveal a crucial function and mechanism for <i>MFN2</i> in regulating MSC differentiation from iPSCs, which will provide new ideas for periodontal tissue engineering and periodontal regenerative treatment by using iPSC-MSCs.</p>\",\"PeriodicalId\":21934,\"journal\":{\"name\":\"Stem cells and development\",\"volume\":\"31 7-8\",\"pages\":\"181-194\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2022-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stem cells and development\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/scd.2021.0316\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/3/11 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem cells and development","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/scd.2021.0316","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/3/11 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
Downregulating MFN2 Promotes the Differentiation of Induced Pluripotent Stem Cells into Mesenchymal Stem Cells through the PI3K/Akt/GSK-3β/Wnt Signaling Pathway.
Understanding the mechanism of the differentiation of induced pluripotent stem cells (iPSCs) into mesenchymal stem cells (MSCs) and promoting the production efficiency of iPSC-derived MSCs (iPSC-MSCs) are critical to periodontal tissue engineering. However, the gene networks that control this differentiation process from iPSCs into MSCs are poorly understood. We demonstrated that MFN2 knockdown showed a positive effect on the triploblastic and MSC differentiation from iPSCs. Activation of the PI3K/Akt signaling pathway by MFN2 knockdown activated the Wnt/β-catenin signaling pathway by inhibiting GSK-3β and reducing β-catenin degradation. Inhibitor of the PI3K/Akt signaling pathway normalized the enhanced efficiency of differentiation into MSCs of MFN2-KD iPSCs and Wnt activator-treated control iPSCs. MFN2-OE iPSCs displayed an opposite phenotype. In conclusion, downregulating MFN2 promotes the differentiation of iPSCs into MSCs by activating the PI3K/Akt/GSK-3β/Wnt signaling pathway. Our results reveal a crucial function and mechanism for MFN2 in regulating MSC differentiation from iPSCs, which will provide new ideas for periodontal tissue engineering and periodontal regenerative treatment by using iPSC-MSCs.
期刊介绍：
Stem Cells and Development is globally recognized as the trusted source for critical, even controversial coverage of emerging hypotheses and novel findings. With a focus on stem cells of all tissue types and their potential therapeutic applications, the Journal provides clinical, basic, and translational scientists with cutting-edge research and findings.
Stem Cells and Development coverage includes:
Embryogenesis and adult counterparts of this process
Physical processes linking stem cells, primary cell function, and structural development
Hypotheses exploring the relationship between genotype and phenotype
Development of vasculature, CNS, and other germ layer development and defects
Pluripotentiality of embryonic and somatic stem cells
The role of genetic and epigenetic factors in development
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