Cell-specific characterization of the placental methylome
Abstract Background 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 methy...
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doaj-9a6410a88154492795169c4116323ce92021-01-10T12:33:42ZengBMCBMC Genomics1471-21642021-01-0122112010.1186/s12864-020-07186-6Cell-specific characterization of the placental methylomeVictor Yuan0Desmond Hui1Yifan Yin2Maria S. Peñaherrera3Alexander G. Beristain4Wendy P. Robinson5BC Children’s Hospital Research InstituteBC Children’s Hospital Research InstituteBC Children’s Hospital Research InstituteBC Children’s Hospital Research InstituteBC Children’s Hospital Research InstituteBC Children’s Hospital Research InstituteAbstract Background 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12864-020-07186-6DNA methylationPlacentaHumanEpigeneticsMicroarrayEPIC array |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Victor Yuan Desmond Hui Yifan Yin Maria S. Peñaherrera Alexander G. Beristain Wendy P. Robinson |
spellingShingle |
Victor Yuan Desmond Hui Yifan Yin Maria S. Peñaherrera Alexander G. Beristain Wendy P. Robinson Cell-specific characterization of the placental methylome BMC Genomics DNA methylation Placenta Human Epigenetics Microarray EPIC array |
author_facet |
Victor Yuan Desmond Hui Yifan Yin Maria S. Peñaherrera Alexander G. Beristain Wendy P. Robinson |
author_sort |
Victor Yuan |
title |
Cell-specific characterization of the placental methylome |
title_short |
Cell-specific characterization of the placental methylome |
title_full |
Cell-specific characterization of the placental methylome |
title_fullStr |
Cell-specific characterization of the placental methylome |
title_full_unstemmed |
Cell-specific characterization of the placental methylome |
title_sort |
cell-specific characterization of the placental methylome |
publisher |
BMC |
series |
BMC Genomics |
issn |
1471-2164 |
publishDate |
2021-01-01 |
description |
Abstract Background 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. Results 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. Conclusions 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. |
topic |
DNA methylation Placenta Human Epigenetics Microarray EPIC array |
url |
https://doi.org/10.1186/s12864-020-07186-6 |
work_keys_str_mv |
AT victoryuan cellspecificcharacterizationoftheplacentalmethylome AT desmondhui cellspecificcharacterizationoftheplacentalmethylome AT yifanyin cellspecificcharacterizationoftheplacentalmethylome AT mariaspenaherrera cellspecificcharacterizationoftheplacentalmethylome AT alexandergberistain cellspecificcharacterizationoftheplacentalmethylome AT wendyprobinson cellspecificcharacterizationoftheplacentalmethylome |
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