Yuan Victor, Hui Desmond, Yin Yifan, Peñaherrera Maria S, Beristain Alexander G, Robinson Wendy P
BC Children's Hospital Research Institute, Vancouver, BC, Canada.
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
BMC Genomics. 2021 Jan 6;22(1):6. doi: 10.1186/s12864-020-07186-6.
DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n = 9) and term (n = 19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at > 850,000 CpGs.
The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation.
Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from GEO (GSE159526), through interactive exploration from the web browser ( https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/ ), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.
DNA甲基化（DNAm）分析已成为表征胎盘甲基化组的有力工具。然而，先前的研究主要集中在整个胎盘组织上，而整个胎盘组织是表观遗传上不同的细胞群体的混合物。在这里，我们使用Illumina EPIC甲基化阵列对孕早期（n = 9）和足月（n = 19）的人类胎盘样本中的四种细胞群体：滋养层细胞、霍夫鲍尔细胞、内皮细胞和基质细胞进行了首次全甲基化组分析，该阵列可对超过85万个CpG位点的DNAm进行定量。
最独特的DNAm图谱是胎盘滋养层细胞和霍夫鲍尔细胞的图谱，滋养层细胞对许多妊娠必需功能至关重要，而霍夫鲍尔细胞是一种罕见的源自胎儿的巨噬细胞群体。细胞特异性DNAm发生在功能相关基因上，包括与胎盘发育和先兆子痫相关的基因。已知的胎盘特异性甲基化标记，如与基因组印记、重复元件低甲基化和胎盘部分甲基化结构域相关的标记，在滋养层细胞中更为明显，而在霍夫鲍尔细胞中通常不存在。最后，我们表征了整个妊娠期的细胞组成和细胞特异性DNAm动态变化。
我们的结果提供了对孕早期和足月妊娠的人类胎盘细胞类型中DNAm的全面分析。这些数据将作为未来胎盘研究的有用DNAm参考，我们通过从GEO（GSE159526）下载、通过网络浏览器（https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/）进行交互式探索以及通过R包planet提供对这些数据的访问，该R包允许直接从胎盘DNAm数据估计细胞组成。
