Human Genomics, Institute of Environmental Science and Research (ESR), Porirua, Wellington, New Zealand.
Malaghan Institute of Medical Research, Wellington, New Zealand.
PLoS One. 2020 Nov 4;15(11):e0241367. doi: 10.1371/journal.pone.0241367. eCollection 2020.
Epigenetics plays a fundamental role in cellular development and differentiation; epigenetic mechanisms, such as DNA methylation, are involved in gene regulation and the exquisite nuance of expression changes seen in the journey from pluripotency to final differentiation. Thus, DNA methylation as a marker of cell identify has the potential to reveal new insights into cell biology. We mined publicly available DNA methylation data with a machine-learning approach to identify differentially methylated loci between different white blood cell types. We then interrogated the DNA methylation and mRNA expression of candidate loci in CD4+, CD8+, CD14+, CD19+ and CD56+ fractions from 12 additional, independent healthy individuals (6 male, 6 female). 'Classic' immune cell markers such as CD8 and CD19 showed expected methylation/expression associations fitting with established dogma that hypermethylation is associated with the repression of gene expression. We also observed large differential methylation at loci which are not established immune cell markers; some of these loci showed inverse correlations between methylation and mRNA expression (such as PARK2, DCP2). Furthermore, we validated these observations further in publicly available DNA methylation and RNA sequencing datasets. Our results highlight the value of mining publicly available data, the utility of DNA methylation as a discriminatory marker and the potential value of DNA methylation to provide additional insights into cell biology and developmental processes.
表观遗传学在细胞发育和分化中起着基本作用；表观遗传机制，如 DNA 甲基化，参与基因调控和从多能性到最终分化过程中观察到的表达变化的精细细微差别。因此，作为细胞身份标志物的 DNA 甲基化有可能为细胞生物学提供新的见解。我们使用机器学习方法挖掘了公开可用的 DNA 甲基化数据，以识别不同白细胞类型之间的差异甲基化位点。然后，我们在来自另外 12 位健康个体（6 名男性，6 名女性）的 CD4+、CD8+、CD14+、CD19+和 CD56+ 分数中对候选位点的 DNA 甲基化和 mRNA 表达进行了检测。像 CD8 和 CD19 这样的“经典”免疫细胞标志物表现出预期的甲基化/表达关联，符合这样的既定理论，即过度甲基化与基因表达的抑制有关。我们还观察到在尚未确定的免疫细胞标志物的位点上存在大量差异甲基化；其中一些位点的甲基化和 mRNA 表达之间存在反向相关性（例如 PARK2、DCP2）。此外，我们在公开的 DNA 甲基化和 RNA 测序数据集中进一步验证了这些观察结果。我们的结果强调了挖掘公开可用数据的价值、DNA 甲基化作为区分标志物的效用以及 DNA 甲基化在提供对细胞生物学和发育过程的额外见解方面的潜在价值。
