Dataset Information

5-Formylcytosine landscapes of human preimplantation embryos at single-cell resolution.

ABSTRACT: Epigenetic dynamics, such as DNA methylation and chromatin accessibility, have been extensively explored in human preimplantation embryos. However, the active demethylation process during this crucial period remains largely unexplored. In this study, we use single-cell chemical-labeling-enabled C-to-T conversion sequencing (CLEVER-seq) to quantify the DNA 5-formylcytosine (5fC) levels of human preimplantation embryos. We find that 5-formylcytosine phosphate guanine (5fCpG) exhibits genomic element-specific distribution features and is enriched in L1 and endogenous retrovirus-K (ERVK), the subfamilies of repeat elements long interspersed nuclear elements (LINEs) and long terminal repeats (LTRs), respectively. Unlike in mice, paired pronuclei in the same zygote present variable difference of 5fCpG levels, although the male pronuclei experience stronger global demethylation. The nucleosome-occupied regions show a higher 5fCpG level compared with nucleosome-depleted ones, suggesting the role of 5fC in organizing nucleosome position. Collectively, our work offers a valuable resource for ten-eleven translocation protein family (TET)-dependent active demethylation-related study during human early embryonic development.

SUBMITTER: Gao Y

PROVIDER: S-EPMC7419013 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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5-Formylcytosine landscapes of human preimplantation embryos at single-cell resolution.

Gao Yun Y Li Lin L Yuan Peng P Zhai Fan F Ren Yixin Y Yan Liying L Li Rong R Lian Ying Y Zhu Xiaohui X Wu Xinglong X Kee Kehkooi K Wen Lu L Qiao Jie J Tang Fuchou F

PLoS biology 20200730 7

Epigenetic dynamics, such as DNA methylation and chromatin accessibility, have been extensively explored in human preimplantation embryos. However, the active demethylation process during this crucial period remains largely unexplored. In this study, we use single-cell chemical-labeling-enabled C-to-T conversion sequencing (CLEVER-seq) to quantify the DNA 5-formylcytosine (5fC) levels of human preimplantation embryos. We find that 5-formylcytosine phosphate guanine (5fCpG) exhibits genomic eleme ...[more]

PMID: 32730243

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Project description:PURPOSEThe purpose of this paper is to study whether human preimplantation embryos regulate endometrial stromal cell (hESC) migration.METHODSPrimary hESCs were isolated from fertile patients undergoing hysterectomy for benign conditions (uterine scar niche n?=?3, dysmenorrhea n?=?2; no hormonal treatment). Migration and proliferation assays were performed by culturing decidualized or non-decidualized hESCs in the presence of embryo conditioned medium (ECM) from high-quality embryos (fragmentation ??20%) or from low-quality embryos (fragmentation >?20%) or in non-conditioned medium from the same dishes (control). ECM samples from 425 individually cultured human embryos were used in this study.RESULTSECM from high-quality embryos, i.e., with a low percentage of fragmentation, actively stimulated decidualized hESC migration (p?<?0.001). This effect was consistent throughout embryonic development from cleavage stage embryos with 2-7 cells (high quality vs. control; p?=?0.036), 8-18 cells (high quality vs. control; p?<?0.001) to morulae (high quality vs. control; p?=?0.003). Additionally, linear regression analysis showed that hESC migration was influenced by embryo quality (fragmentation, ? -?0.299; p?=?0.025) and not developmental stage (cell number, ? 0.177; p?=?0.176) or maternal age (? -?0.036; p?=?0.78). Opposite to decidualized hESCs, the migration response of non-decidualized hESCs was inhibited by ECM from high-quality embryos (p?=?0.019). ECM from low-quality embryos, i.e., with a high percentage of fragmentation, did not cause an altered migration response in decidualized hESCs (p?=?0.860) or non-decidualized hESCs (p?=?0.986). Furthermore, ECM of both high- and low-quality human embryos did not influence the number of proliferating cells (p?=?0.375) and the cell cycle time (p?=?0.297) of non-decidualized or decidualized hESCs.CONCLUSIONThis study reveals a mechanism by which high-quality human preimplantation embryos actively interact with the endometrium to increase their chances of successful implantation.

Dataset Information

5-Formylcytosine landscapes of human preimplantation embryos at single-cell resolution.

Publications

5-Formylcytosine landscapes of human preimplantation embryos at single-cell resolution.

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