Reconstituting the transcriptome and DNA methylome landscapes of human implantation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA431392 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6506270_1.fastq.gz | Fastqsanger.gz | |||
| SRR6506270_2.fastq.gz | Fastqsanger.gz | |||
| SRR6506280_1.fastq.gz | Fastqsanger.gz | |||
| SRR6506280_2.fastq.gz | Fastqsanger.gz | |||
| SRR6506290_1.fastq.gz | Fastqsanger.gz |
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Project description:Implantation is a milestone event during mammalian embryogenesis. Implantation failure is a nonnegligible cause of human early pregnancy loss. Due to the extreme difficulty of obtaining in vivo human early post-implantation embryos, it remains elusive how the gene regulatory network and epigenetic mechanisms control human embryo implantation. Here, combining an in vitro culture system for human post-implantation development and single-cell omics sequencing technologies, over 8,000 individual cells from 65 human peri-implantation embryos were systematically analyzed. Unsupervised dimensionality reduction and clustering algorithm of the transcriptome data show stepwise implantation routes for the epiblast (EPI), primitive endoderm (PE), and trophectoderm (TE) lineages, suggesting robust preparation for the proper establishment of a mother-to-offspring connection during implantation. Female embryos showed initiation of random X chromosome inactivation based on analysis of parental allele-specific expression of X chromosome-linked genes during implantation. Surprisingly, by the single-cell Trio-Seq (scTrio-Seq) analysis, the genome re-methylation of PE lineage was shown to be much slower than those of both EPI and TE lineages during implantation process, indicating distinct DNA methylome re-establishment features between EPI and PE although both of which were derived from inner cell mass (ICM). Collectively, our work paves the way for understanding the complex molecular mechanisms that regulate human embryo implantation, offering new insights and future efforts in early embryonic development and reproductive medicine.
2019-07-11 | GSE109555 | GEO
Project description:Implantation is a milestone event during mammalian embryogenesis. Due to the extreme difficulty of obtaining in vivo human early post-implantation embryos, the gene regulatory network and epigenetics controlling human embryo implantation remains elusive. Here, combining an in vitro culture system for human post-implantation development and single-cell omics sequencing technologies, over 10,000 single cells at five representative stages of pre/post-implantation development were systematically analyzed. Unsupervised dimensionality reduction and clustering algorithm of the transcriptome data show stepwise implantation routes for the epiblast, primitive endoderm, and trophectoderm lineages, suggesting preparation for the establishment of a mother-to-offspring connection after implantation. Female embryos showed asynchronous progress of dosage loss of X chromosomes during implantation. Furthermore, using the single cell trio-Seq (scTrio-Seq) strategy, re-methylation of the genomes of all the three lineages was unambiguously revealed. Surprisingly, the genome re-methylation of PE lineage were much slower than both EPI and TE lineages during the implantation process, indicating distinct methylome features between EPI and PE although both of which were derived from ICM. Collectively, our work paves the way for understanding the complex molecular mechanisms that regulate human embryo implantation, informing new insights and future efforts in early embryonic development and reproductive medicine.
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Project description:We report the application of MeRIP sequencing technology for high-throughput profiling of m6A methylome in breast cancer cells. Comparison of m6A methylome between METTL3-WT and METTL3-K177Q reconstituting cells revealed the following findings: 1) Significant global alteration of methylation sites due to K177Q mutation (termed as KQ-m6A signature). 2) GO analysis of the differential m6A-MeRIP candidates enriched pathways involved in chromatin modification, RNA splicing, DNA damage, cell cycle, and autophagy, consistent with a critical role of m6A-mediated nuclear biological activities and highlighted generally recognized cellular events associated with tumorigenesis. 3) we dissected potential mechanistic clues explaining the attenuated invasive phenotype in METTL3K177Q reconstituting cells.
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Project description:Separate sexes in dioecious plants display different morphology and physiological characteristics. The differences between the two sexes lie in their highly differentiated floral characteristics and in sex-related phenotype, which is genetically determined and epigenetically modified. In dioecious papaya (Carica papaya L.), global comparisons of epigenetic DNA methylation and gene expressions were still limited. We conducted bisulfite sequencing of early-stage flowers grown in three seasons (spring, summer and winter) and compared their methylome and transcriptome profiles to investigate the differential characteristics of male and female in papaya. Methylation variances between female and male papaya were conserved among three different seasons. However, combined genome-scale transcriptomic evidence revealed that most methylation variances did not have influence on the expression profiles of neighboring genes, and the differentially expressed genes were most overrepresented in phytohormone signal transduction pathways. Further analyses showed diverse stress-responsive methylation alteration in male and female flowers. Male flower methylation was more responsive to stress whereas female flower methylation varied less under stress. Early flowering of male papaya in spring might be associated with the variation in the transcription of CpSVP and CpAP1 coinciding with their gene-specific hypomethylation. These findings provide insights into the sex-specific DNA methylation and gene expression landscapes of dioecious papaya and a foundation to investigate the correlation between differentiated floral characteristics and their candidate genes.
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Project description:Unlike the better-studied aberrant epigenome in the tumor, the clinicopathologic impact of DNA methylation in the tumor microenvironment (TME), especially the contribution from cancer-associated fibroblasts (CAFs), remains elusive. CAFs exhibit profound patient-to-patient tumorigenic heterogeneity. We asked whether such heterogeneity may be exploited to quantify the level of TME malignancy. We developed a robust and efficient methylome/transcriptome co-analytical system for CAFs and paired normal fibroblasts (NFs) from non-small-cell lung cancer patients. We found 14,781 CpG sites of CAF/NF differential methylation, of which 3,707 sites showed higher methylation changes in ever-smokers than in nonsmokers. Concomitant CAF/NF differential gene expression analysis pointed to a subset of 54 smoking-associated CpG sites with strong methylation-regulated gene expression. A methylation index that summarizes the β values of these CpGs was built for NF/CAF discrimination (MIND) with high sensitivity and specificity. The potential of MIND in detecting premalignancy across individual patients was shown. MIND succeeded in predicting tumor recurrence in multiple lung cancer cohorts without reliance on patient survival data, suggesting that the malignancy level of TME may be effectively graded by this index. Precision TME grading may provide additional pathological information to guide cancer prognosis and open up more options in personalized medicine.
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Project description:BackgroundBreast intraductal papilloma (IP) is mainly caused by the abnormal proliferation of ductal epithelial cells. Tree shrews have potential as an animal model for the study of breast tumours; however, little is known regarding the transcriptome and DNA methylome landscapes of breast IP in tree shrews. In this research, we conducted whole-genome DNA methylation and transcriptome analyses of breast IP and normal mammary glands in tree shrews.MethodsDNA methylation profiles were generated from the whole-genome bisulfite sequencing and whole-transcriptome landscapes of IP and control groups of tree shrews through strand-specific library construction and RNA sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses and gene set enrichment analysis were performed. Spearman's correlation analysis was used to identify statistical relationships between gene expression and DNA methylation.ResultsA genome-wide perspective of the epigenetic regulation of protein-coding genes in breast IP in tree shrews was obtained. The methylation levels at CG sites were considerably higher than those at CHG or CHH sites, and were highest in gene body regions. In total, 3,486, 82 and 361 differentially methylated regions (DMRs) were identified in the context of CG, CHG, and CHH, respectively, and 701 differentially methylated genes (DMGs) were found. Further, through transcriptomic analysis, 62 differentially expressed genes, 50 long noncoding RNAs, and 32 circular RNAs were identified in breast IP compared to normal mammary glands. Correlation analysis between the DNA methylation and transcriptome data revealed that 25 DMGs were also differentially expressed genes, among which the expression levels of 9 genes were negatively correlated with methylation levels in gene body regions. Importantly, integrated analysis identified 3 genes (PDZ domain-containing 1, ATPase plasma membrane Ca2+ transporting 4 and Lymphocyte cytosolic protein 1) that could serve as candidates for further study of breast IP in tree shrews.ConclusionsThis research has unearthed the comprehensive landscape of the transcriptome and DNA methylome of spontaneous IP in tree shrews, as well as candidate tumorigenesis related genes in IP. These results will contribute to the use of tree shrews in animal models of breast tumours.
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Project description:Germ cells are vital for transmitting genetic information from one generation to the next and for maintaining the continuation of species. Here, we analyze the transcriptome of human primordial germ cells (PGCs) from the migrating stage to the gonadal stage at single-cell and single-base resolutions. Human PGCs show unique transcription patterns involving the simultaneous expression of both pluripotency genes and germline-specific genes, with a subset of them displaying developmental stage-specific features. Furthermore, we analyze the DNA methylome of human PGCs and find global demethylation of their genomes. Approximately 10-11 weeks after gestation, the PGCs are nearly devoid of any DNA methylation; with only 7.8% and 6.0% of the median methylation levels in male and female PGCs, respectively. Our work paves the way toward deciphering the complex epigenetic reprogramming of the germline with the aim of restoring totipotency in fertilized oocytes.
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