在PBMCs和捐赠者匹配的iPSCs中对DNA甲基化的表征表明,在干细胞重编程过程中甲基化被重置
Xylena Reed1,2, Cory A Weller2,3, Sara Saez-Atienzar4,5
1Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
bioRxiv : the preprint server for biology
|December 23, 2024
概括
与衰老相关的DNA甲基化在诱导多能干细胞 (iPSC) 中在很大程度上被重置. 这项研究表明,iPSC中的表观遗传钟反映了较早的生物年龄,在每个细胞类型的甲基化位点上具有独特的遗传影响.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因组学就是基因组学.
- 干细胞生物学 干细胞生物学
背景情况:
- 基因甲基化是影响细胞功能的关键表观遗传机制,受年龄,环境和遗传学的影响.
- 年龄是神经退行性疾病的主要风险因素,因此了解与衰老相关的表观遗传变化在细胞重编程后如何持续至关重要.
- 诱导多能干细胞 (iPSC) 提供了一个研究细胞衰老和疾病的模型,但它们的表观遗传忠实性需要研究.
研究的目的:
- 为了确定与衰老相关的DNA甲基化特征是否保留在来自外围血液单核细胞 (PBMC) 的诱导多能干细胞 (iPSC) 中.
- 研究细胞重编程对表观遗传时钟的影响,并确定iPSC和PBMC中受遗传影响的甲基化位点.
主要方法:
- 用全基因组DNA甲基化阵列来分析PBMCs (n=99) 和它们衍生的iPSCs.
- 进行了全表观基因组关联研究 (EWAS),以评估两种细胞类型的表观基因年龄.
- 甲基化定量特征位点 (methQTL) 分析进行,以确定受遗传影响的甲基化位点.
主要成果:
- 与其父母PBMC相比,iPSC的表观遗传时钟在很大程度上被重置到较早的甲基化年龄.
- 在iPSC和PBMC之间观察到表观遗传年龄特征的显著差异.
- 在每个细胞类型中确定了一组独特的甲基化定量特征位点 (methQTL),表明细胞特异性DNA甲基化的遗传调节.
结论:
- 将细胞重新编程到iPSC状态基本上会重置与年龄相关的DNA甲基化模式.
- 在iPSC的表观遗传年龄并不完全重复起源的体细胞的表观遗传年龄.
- 遗传学在塑造DNA甲基化模式方面发挥着重要作用,观察到细胞类型特定的methQTLs.
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