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

IF 3.5 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY BMC Genomics Pub Date : 2024-11-06 DOI:10.1186/s12864-024-10986-9
Hidehiro Toh, Hiroaki Okae, Kenjiro Shirane, Tetsuya Sato, Hirotaka Hamada, Chie Kikutake, Daisuke Saito, Takahiro Arima, Hiroyuki Sasaki, Mikita Suyama
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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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人类胎盘和滋养层干细胞中部分甲基化结构域的表观遗传动态。
背景:胎盘对母体和发育中胎儿之间的营养交换和激素分泌至关重要,是表观遗传学研究的宝贵模型。对人类胎盘进行的大多数表观遗传学研究都使用了足月妊娠的整个胎盘,并发现了部分甲基化结构域(PMDs)的存在。然而,这些在大多数体细胞中通常不存在的结构域在胎盘中的起源仍不清楚:结果:通过全基因组亚硫酸氢盐测序和组蛋白 H3 修饰分析,我们生成了妊娠头三个月和足月人类细胞滋养层母细胞以及人类滋养层母细胞干细胞的表观遗传学图谱。我们的研究特别关注 PMD。我们发现,在滋养层外胚层重编程过程中,可能形成 PMD 的基因组区域对全局 DNA 去甲基化具有抵抗力,而 PMD 是通过核薄层附近凝聚染色质内的缓慢甲基化过程产生的。此外,我们还发现细胞滋养层细胞和滋养层干细胞中的PMDs在组蛋白H3修饰方面存在显著差异:我们的研究结果表明,时空基因组特征塑造了人类胎盘的巨碱基DNA甲基化模式,包括PMDs,并强调了人类细胞滋养层母细胞和滋养层干细胞之间在PMDs上的明显差异。这些发现增进了我们对胎盘生物学的了解,为进一步研究人类发育和相关疾病提供了基础。
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来源期刊
BMC Genomics
BMC Genomics 生物-生物工程与应用微生物
CiteScore
7.40
自引率
4.50%
发文量
769
审稿时长
6.4 months
期刊介绍: BMC Genomics is an open access, peer-reviewed journal that considers articles on all aspects of genome-scale analysis, functional genomics, and proteomics. BMC Genomics is part of the BMC series which publishes subject-specific journals focused on the needs of individual research communities across all areas of biology and medicine. We offer an efficient, fair and friendly peer review service, and are committed to publishing all sound science, provided that there is some advance in knowledge presented by the work.
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