本文選題：5-氮胞苷　切入點(diǎn)：間充質(zhì)干細(xì)胞　出處：《浙江大學(xué)》2010年碩士論文

【摘要】： 具有多向分化潛能的骨髓間充質(zhì)干細(xì)胞(Mesenchymal stem cells,MSCs)是組織工程良好的細(xì)胞種子來源,然而使干細(xì)胞高效地向預(yù)定的方向分化還是個(gè)很大的挑戰(zhàn),這就需要我們充分了解干細(xì)胞分化的調(diào)節(jié)機(jī)制。除了傳統(tǒng)的轉(zhuǎn)錄因子調(diào)節(jié),表觀遺傳修飾也在干細(xì)胞分化調(diào)控中也起著十分重要的作用,DNA甲基化修飾是表觀遺傳調(diào)控的主要方式之一。本文以MSCs成骨分化為模型,利用DNA甲基化抑制劑——5-氮胞苷研究了DNA甲基化對(duì)MSCs成骨分化的影響。在成骨分化誘導(dǎo)前用5-氮胞苷預(yù)處理MSCs 24小時(shí),其成骨分化效率明顯提高,并伴隨著基因組整體水平上DNA甲基化修飾的減少。在單基因水平上,我們又檢測(cè)了成骨分化重要調(diào)控基因Dlx5上甲基化修飾水平的變化,發(fā)現(xiàn)5-氮胞苷預(yù)處理后,Dlx5基因的“CpGisland shore”處甲基化水平降低。本文充分證明了DNA甲基化修飾在MSCs分化中的作用,為MSCs未來的研究和應(yīng)用提供了重要依據(jù)和方法。
[Abstract]:Bone marrow mesenchymal stem cells (MSCs), which have the potential of multiple differentiation, are good seed sources for tissue engineering. However, it is still a challenge to differentiate the stem cells efficiently in a predetermined direction. This requires us to fully understand the regulatory mechanisms of stem cell differentiation, in addition to traditional transcription factor regulation, Epigenetic modification also plays an important role in the regulation of stem cell differentiation. DNA methylation is one of the main methods of epigenetic regulation. The effect of DNA methylation on MSCs osteogenic differentiation was studied by using 5-azacytidine, a DNA methylation inhibitor. The osteogenic differentiation efficiency was significantly improved after pretreatment of MSCs with 5-azacytidine for 24 hours before osteogenesis induction. At the single gene level, we also detected the change of methylation modification level on Dlx5, an important regulation gene of osteogenic differentiation. It was found that the methylation level at "CpGisland shore" of Dlx5 gene decreased after pretreatment with 5-azacytidine. The role of DNA methylation in MSCs differentiation was fully demonstrated, which provided an important basis and method for the future study and application of MSCs.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R329

【引證文獻(xiàn)】

相關(guān)博士學(xué)位論文 前1條

1 馮志遠(yuǎn);寡核苷酸（ODN）促成骨細(xì)胞增殖活化的作用及機(jī)制研究[D];吉林大學(xué);2011年

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本文編號(hào)：1688490