Epigenetic dynamics of partially methylated domains in human placenta and trophoblast stem cells

Abstract Background The placenta is essential for nutrient exchange and hormone production between the mother and the developing fetus and serves as an invaluable model for epigenetic research. Most epigenetic studies of the human placenta have used whole placentas from term pregnancies and have ide...

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Main Authors: Hidehiro Toh, Hiroaki Okae, Kenjiro Shirane, Tetsuya Sato, Hirotaka Hamada, Chie Kikutake, Daisuke Saito, Takahiro Arima, Hiroyuki Sasaki, Mikita Suyama
Format: Article
Language:English
Published: BMC 2024-11-01
Series:BMC Genomics
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Online Access:https://doi.org/10.1186/s12864-024-10986-9
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author Hidehiro Toh
Hiroaki Okae
Kenjiro Shirane
Tetsuya Sato
Hirotaka Hamada
Chie Kikutake
Daisuke Saito
Takahiro Arima
Hiroyuki Sasaki
Mikita Suyama
author_facet Hidehiro Toh
Hiroaki Okae
Kenjiro Shirane
Tetsuya Sato
Hirotaka Hamada
Chie Kikutake
Daisuke Saito
Takahiro Arima
Hiroyuki Sasaki
Mikita Suyama
author_sort Hidehiro Toh
collection DOAJ
description Abstract Background The placenta is essential for nutrient exchange and hormone production between the mother and the developing fetus and serves as an invaluable model for epigenetic research. Most epigenetic studies of the human placenta have used whole placentas from term pregnancies and have identified the presence of partially methylated domains (PMDs). However, the origin of these domains, which are typically absent in most somatic cells, remains unclear in the placental context. Results Using whole-genome bisulfite sequencing and analysis of histone H3 modifications, we generated epigenetic profiles of human cytotrophoblasts during the first trimester and at term, as well as human trophoblast stem cells. Our study focused specifically on PMDs. We found that genomic regions likely to form PMDs are resistant to global DNA demethylation during trophectoderm reprogramming, and that PMDs arise through a slow methylation process within condensed chromatin near the nuclear lamina. In addition, we found significant differences in histone H3 modifications between PMDs in cytotrophoblasts and trophoblast stem cells. Conclusions Our findings suggest that spatiotemporal genomic features shape megabase-scale DNA methylation patterns, including PMDs, in the human placenta and highlight distinct differences in PMDs between human cytotrophoblasts and trophoblast stem cells. These findings advance our understanding of placental biology and provide a basis for further research into human development and related diseases.
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spelling doaj-art-38a1cd4b425b42a799cbcef9e883d6e72025-08-20T02:13:27ZengBMCBMC Genomics1471-21642024-11-0125111110.1186/s12864-024-10986-9Epigenetic dynamics of partially methylated domains in human placenta and trophoblast stem cellsHidehiro Toh0Hiroaki Okae1Kenjiro Shirane2Tetsuya Sato3Hirotaka Hamada4Chie Kikutake5Daisuke Saito6Takahiro Arima7Hiroyuki Sasaki8Mikita Suyama9Advanced Genomics Center, National Institute of GeneticsDepartment of Trophoblast Research, Institute of Molecular Embryology and Genetics, Kumamoto UniversityDepartment of Genome Biology, Graduate School of Medicine, Osaka UniversityBiomedical Research Center, Faculty of Medicine, Saitama Medical UniversityDepartment of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of MedicineDivision of Bioinformatics, Medical Institute of Bioregulation, Kyushu UniversityDivision of Bioinformatics, Medical Institute of Bioregulation, Kyushu UniversityDepartment of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of MedicineDivision of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu UniversityDivision of Bioinformatics, Medical Institute of Bioregulation, Kyushu UniversityAbstract Background The placenta is essential for nutrient exchange and hormone production between the mother and the developing fetus and serves as an invaluable model for epigenetic research. Most epigenetic studies of the human placenta have used whole placentas from term pregnancies and have identified the presence of partially methylated domains (PMDs). However, the origin of these domains, which are typically absent in most somatic cells, remains unclear in the placental context. Results Using whole-genome bisulfite sequencing and analysis of histone H3 modifications, we generated epigenetic profiles of human cytotrophoblasts during the first trimester and at term, as well as human trophoblast stem cells. Our study focused specifically on PMDs. We found that genomic regions likely to form PMDs are resistant to global DNA demethylation during trophectoderm reprogramming, and that PMDs arise through a slow methylation process within condensed chromatin near the nuclear lamina. In addition, we found significant differences in histone H3 modifications between PMDs in cytotrophoblasts and trophoblast stem cells. Conclusions Our findings suggest that spatiotemporal genomic features shape megabase-scale DNA methylation patterns, including PMDs, in the human placenta and highlight distinct differences in PMDs between human cytotrophoblasts and trophoblast stem cells. These findings advance our understanding of placental biology and provide a basis for further research into human development and related diseases.https://doi.org/10.1186/s12864-024-10986-9Human cytotrophoblastsHuman trophoblast stem cellsPartially methylated domainsMethylomes
spellingShingle Hidehiro Toh
Hiroaki Okae
Kenjiro Shirane
Tetsuya Sato
Hirotaka Hamada
Chie Kikutake
Daisuke Saito
Takahiro Arima
Hiroyuki Sasaki
Mikita Suyama
Epigenetic dynamics of partially methylated domains in human placenta and trophoblast stem cells
BMC Genomics
Human cytotrophoblasts
Human trophoblast stem cells
Partially methylated domains
Methylomes
title Epigenetic dynamics of partially methylated domains in human placenta and trophoblast stem cells
title_full Epigenetic dynamics of partially methylated domains in human placenta and trophoblast stem cells
title_fullStr Epigenetic dynamics of partially methylated domains in human placenta and trophoblast stem cells
title_full_unstemmed Epigenetic dynamics of partially methylated domains in human placenta and trophoblast stem cells
title_short Epigenetic dynamics of partially methylated domains in human placenta and trophoblast stem cells
title_sort epigenetic dynamics of partially methylated domains in human placenta and trophoblast stem cells
topic Human cytotrophoblasts
Human trophoblast stem cells
Partially methylated domains
Methylomes
url https://doi.org/10.1186/s12864-024-10986-9
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