Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Placental and Immune Cell DNA Methylation Reference Panel for Bulk Tissue Cell Composition Estimation in Epidemiological Studies

ABSTRACT: To distinguish DNA methylation (DNAm) from cell proportion changes in whole placental villous tissue research, we developed a robust cell type-specific DNAm reference to estimate cell composition. We collated new and existing cell type DNAm profiles quantified via Illumina EPIC or 450k microarrays. To estimate cell composition, we deconvoluted whole placental samples (n=36) with robust partial correlation based on the top 30 hyper- and hypomethylated sites identified per cell type. To test deconvolution performance, we evaluated RMSE in predicting principal components of DNAm variation in 204 external placental samples. We analyzed DNAm profiles (n=368,435 sites) from 12 cell types: cytotrophoblasts (n=18), endothelial cells (n=19), Hofbauer cells (n=26), stromal cells (n=21), syncytiotrophoblasts (n=4), six lymphocyte types (n=36), and nucleated red blood cells (n=11). Median cell composition was consistent with placental biology: 60.9% syncytiotrophoblast, 17.3% stromal, 8.8% endothelial, 3.7% cytotrophoblast, 3.7% Hofbauer, 1.7% nucleated red blood cells, and 1.2% neutrophils. Our expanded reference outperformed an existing reference in predicting DNAm variation (PC1, 15.4% variance explained, IQR=21.61) with cell composition estimates (RMSEP: 8.62 vs. 10.79, p-value<0.001). This cell type reference can robustly estimate cell composition from whole placental DNAm data to detect important cell types, reveal biological mechanisms, and improve causal inference.

ORGANISM(S): Homo sapiens

PROVIDER: GSE271697 | GEO | 2024/12/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cell-specific Characterization of the Placental Methylome

Project description: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 dbGAP (phs002013.v1.p1), 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.

2020-10-21 | GSE159526 | GEO

DNA methylation analysis of placenta samples exposed to maternal smoking during pregnancy

Project description:Epigenome-wide profiling of placental DNAm in samples obtained from 72 smokers enrolled in the VCSIP RCT: NCT03203603 (35 supplemented with placebo, 37 supplemented with vitamin C) and 24 never-smokers for reference.

2021-09-20 | GSE169598 | GEO

Methylome of Fetal and Maternal Monocytes and Macrophages at the Feto-Maternal Interface

Project description:Maternal and fetal monocytes and tissue macrophages (decidual macrophages, Hofbauer cells) at the feto-maternal interface have different methylome. Paired and balanced design. We compared maternal blood monocytes (MB) vs. cord blood monocytes (CB), maternal blood monocytes (MB) vs. decidual macrophages (Deci), cord blood monocytes (CB) vs placental macrophages (villi) and decidual macrophages (Deci) vs. placental macrophages (villi).

2011-11-15 | E-GEOD-31680 | biostudies-arrayexpress

Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity

Project description:Maternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many mediated by in utero microglial programming. As microglia remain inaccessible throughout development, identification of noninvasive biomarkers reflecting fetal brain microglial programming could permit screening and intervention. We used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells) in a mouse model of maternal diet-induced obesity, and single-cell RNA-seq to demonstrate shared transcriptional programs. Comparison with human datasets demonstrated conservation of placental resident macrophage signatures between mice and humans. Single-cell RNA-seq identified common alterations in fetal microglial and Hofbauer cell gene expression induced by maternal obesity, as well as sex differences in these alterations. We propose that Hofbauer cells, which are easily accessible at birth, provide novel insights into fetal brain microglial programs, and may facilitate the early identification of offspring vulnerable to neurodevelopmental disorders in the setting of maternal exposures.

2024-06-05 | GSE252343 | GEO

CD74 downregulation in placental macrophages and its influence on trophoblast cells.

Project description:Preeclampsia is a disease of pregnant women, which is characterized by hypertension, proteinuria and chronic inflammation. There is a growing body of evidence that cause of preeclampsia lies within immunological aspect of pregnancy. This study aimed to analyze the role of CD74 in preeclampsia with a focus on its influence on communication between placental macrophages (Hofbauer cells) and trophoblasts. We have found CD74 to be highly dysregulated in preeclamptic placenta by real-time RT-PCR and Western blot methods. We identified Hofbauer cells to express the highest levels of CD74 in placenta by immunofluorescence and flow cytometry and that CD74 in preeclamptic Hofbauer cells is lower than in controls. We have performed a transcriptome analysis on human blood monocyte-derived macrophages that were non- or IL-4-activated and treated with small interfering RNA against CD74 (siRNA CD74) or non-targeting siRNA (siRNA non-targeting) as control.

2015-04-29 | E-MTAB-3309 | biostudies-arrayexpress

DNA Methylation Profiling in Mummified Human Remains from the Eighteenth-Century

Project description:Reconstruction of ancient epigenomes by DNA methylation (DNAm) can shed light into the composition of cell types, disease states, and age at death. However, such analysis is hampered by impaired DNA quality and little is known how decomposition affects DNAm. In this study, we determined if EPIC Illumina BeadChip technology is applicable for specimen from mummies of the 18th century CE. Overall, the signal intensity on the microarray was extremely low, but for one of two samples we detected characteristic DNAm signals in a subset of CG dinucleotides (CpGs), which were selected with a stringent processing pipeline. Using only these CpGs we could train epigenetic signatures with reference DNAm profiles of multiple tissues and our predictions were in line with the fact that the specimen was lung tissue of a female 28-year-old donor. Thus, we provide proof of principle that Illumina BeadChips are applicable for DNAm profiling in ancient samples.

2021-08-04 | GSE169595 | GEO

Transcriptomic Analysis of Hofbauer Cells from Human Placental Tissue Infected with HIV, CMV, and ZIKV

Project description:This study involves the isolation of Hofbauer cells from human placental tissue at different gestation periods and their infection with HIV, CMV, and ZIKV. The transcriptomic profiles of these infected cells were analyzed using RNA-sequencing to identify differentially expressed genes and pathways.

2024-09-20 | GSE274414 | GEO

Impact of red blood cells on genome-wide DNA methylation and expression analyses of cord blood hematopoietic cells

Project description:Genome-wide DNA methylation (DNAm) studies have been extremely useful to understand hematopoiesis in humans. For cell-specific epigenetic studies, fluorescence-activated cell sorting (FACS) is the gold standard technique to isolate homogeneous cell populations of interest. However, in cord blood, the DNAm signature of isolated hematopoietic cells may be significantly altered by heterotopic interactions with nucleated red blood cells (nRBCs) that go undetected during conventional cell sorting. Using the Illumina 450K array, genome-wide DNAm profiles of the following cell types were obtained: (1) T lymphocytes, monocytes, and nRBCs isolated using a “standard” strategy lacking exclusion for erythroid lineage markers; and (2) CD4 and CD8 T lymphocytes, B lymphocytes, Natural Killer (NK) cells, granulocytes, monocytes, and nRBCs isolated using a “stringent” strategy formally excluding erythroid lineage-specific markers. DNAm profiles of cord blood cells isolated by the standard sorting strategy showed significant heterotopic cross-contamination between cell populations, whereas the cord blood cells sorted by the stringent strategy displayed DNAm profiles more consistent with their expected hematopoietic lineage relationships.

2015-10-02 | GSE68456 | GEO

Maternal weight affects placental DNA methylation of genes invovled in metabolic pathways in the common marmoset monkey (Callithrix jacchus)

Project description:Accumulating evidence suggests that dysregulation of placental DNA methylation (DNAm) is a mechanism linking maternal weight during pregnancy to metabolic programming outcomes. The common marmoset, Callithrix jaccus, is a platyrrhine primate species that has provided much insight into studies of the primate placenta, maternal condition, and metabolic programming, yet the relationships between maternal weight and placental DNAm are unknown. Here, we report genome-wide DNAm from term marmoset placentas using reduced representation bisulfite sequencing. We identified 74 genes whose DNAm pattern is associated with maternal weight during gestation. These genes are predominantly involved in energy metabolism and homeostasis, including regulation of glycolytic and lipid metabolic processes pathways.

2020-01-07 | GSE143200 | GEO

DNA methylation profiles of human umbilical vein endothelial cells (HUVECs)

Project description:Replicative senescence has major impact on function and integrity of cell preparations. DNA-methylation (DNAm) changes are continuously acquired at specific CpG dinucleotides during in vitro culture. Such modifications can be used to estimate the state of cellular senescence for quality control of cell preparations. It is however unclear how senescence-associated DNAm changes are regulated and if they occur simultaneously throughout cell populations. In this study, we analyzed global DNAm profiles of human mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVEC) to demonstrate that senescence-associated DNAm changes are overall similar in these different cell types. Subsequently, an Epigenetic-Senescence-Signature, based on six CpGs, was either analyzed by pyrosequencing or by barcoded bisulfite amplicon sequencing. There was a good correlation between predicted and real passage numbers in bulk populations of MSCs (R² = 0.67) and HUVECs (R² = 0.97).

2017-02-20 | GSE82234 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data