Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1191977 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31547417_1.fastq.gz | Fastqsanger.gz | |||
| SRR31547417_2.fastq.gz | Fastqsanger.gz | |||
| SRR31547418_1.fastq.gz | Fastqsanger.gz | |||
| SRR31547418_2.fastq.gz | Fastqsanger.gz | |||
| SRR31547419_1.fastq.gz | Fastqsanger.gz |
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Project description:Understanding mammalian preimplantation development, particularly in humans, at the proteomic level remains limited. Here, we applied our Comprehensive Solution of Ultrasensitive Proteome Technology to measure the proteomic profiles of oocytes and early embryos, and identified nearly 8,000 proteins in humans and over 6,300 proteins in mice. We observed distinct proteomic dynamics before and around zygotic genome activation (ZGA) between the two species. Integrative analysis with translatome data revealed extensive divergence between translation activation and protein accumulation. Multi-omic analysis indicated that ZGA transcripts contribute to protein accumulation in blastocysts. Consequently, we identified several transcriptional regulators critical for early development in mice, thereby linking ZGA to the first lineage specification. Furthermore, single-embryo proteomics of poor quality embryos from over 100 patient-couples provided insights into preimplantation development failure. Our study may contribute to reshaping the framework of mammalian preimplantation development and opening new avenues for addressing human infertility.
2024-12-04 | GSE283213 | GEO
Project description:Mammalian preimplantation development is a complex process involving dramatic changes in the transcriptional architecture. Through single-cell RNA-sequencing (RNA-seq), we report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos. Based on single nucleotide variants (SNVs) in blastomere mRNAs and paternal-specific SNPs, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25-53%). By weighted gene co-expression network analysis (WGCNA), we find that each developmental stage can be concisely delineated by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation, and metabolism in a step-wise fashion from cleavage to morula. Cross-species comparisons reveal that the majority of human stage-specific modules (7 out of 9) are remarkably preserved, only to diverge in developmental specificity and timing in mice. We further identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely key players in driving mammalian preimplantation development. Collectively, we demonstrate that mammalian preimplantation development is orchestrated by evolutionarily conserved genetic programs that diverge in developmental timing. Our results provide a valuable resource to dissect gene regulatory mechanism underlying progressive development of early mammalian embryos. single-cell RNA-seq of human and mouse blastomeres
2013-07-29 | E-GEOD-44183 | biostudies-arrayexpress
Project description:Lineage specification and X chromosome dosage compensation are two crucial biological processes that occur during preimplantation embryonic development. While these processes have been studied extensively in mice and humans, they are less understood in other species. This study aims to provide fundamental insights into bovine preimplantation development using single-cell RNA-sequencing. The study analyzes the transcriptomes of 286 individual cells and reveals that bovine trophectoderm/inner cell mass transcriptomes diverge at the early blastocyst stage, after cavitation but before blastocyst expansion. The study also identifies transcriptomic markers and provides the timing of lineage specification events in the bovine embryo. Moreover, the study confirms the occurrence of X chromosome dosage compensation from morula to middle blastocyst and reveals that this compensation results from downregulation of X-linked genes in female embryonic cells. The transcriptional atlas generated by this study is expected to be widely useful in improving our understanding of mammalian early embryo development.
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Project description:Comparative transcriptomic and proteomic analyses provide insights into functional genes for hypoxic adaptation in embryos of Tibetan chickens
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Project description:Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation (ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, and the abnormal phenotypes could be recapitulated by overexpression of H3K18R mutation and rescued by addition of Lac-CoA. By profiling the landscape of H3K18lac in human and mouse preimplantation embryos, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and corelates with their expressions. Taken together, we demonstrate the important role for lactate in major ZGA via H3K18lac, showing a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.
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Project description:Mammalian preimplantation development is associated with marked metabolic robustness, and embryos can develop under a wide variety of nutrient conditions, including even the complete absence of soluble amino acids. Here we show that mouse embryonic stem cells (ESCs) capture the unique metabolic state of preimplantation embryos and proliferate in the absence of several essential amino acids. Amino acid independence is enabled by constitutive uptake of exogenous protein through macropinocytosis, alongside a robust lysosomal digestive system. Following transition to more committed states, ESCs reduce digestion of extracellular protein and instead become reliant on exogenous amino acids. Accordingly, amino acid withdrawal selects for ESCs that mimic the preimplantation epiblast. More broadly, we find that all lineages of preimplantation blastocysts exhibit constitutive macropinocytic protein uptake and digestion. Taken together, these results highlight exogenous protein uptake and digestion as an intrinsic feature of preimplantation development and provide insight into the catabolic strategies that enable embryos to sustain viability before implantation.
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Project description:In mammals, extensive chromatin reorganization is essential for reprogramming terminally committed gametes to a totipotent state during preimplantation development. However, the global chromatin landscape and its dynamics in this period remain unexplored. Here we report a genome-wide map of accessible chromatin in mouse preimplantation embryos using an improved assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) approach with CRISPR/Cas9-assisted mitochondrial DNA depletion. We show that despite extensive parental asymmetry in DNA methylomes, the chromatin accessibility between the parental genomes is globally comparable after major zygotic genome activation (ZGA). Accessible chromatin in early embryos is widely shaped by transposable elements and overlaps extensively with putative cis-regulatory sequences. Unexpectedly, accessible chromatin is also found near the transcription end sites of active genes. By integrating the maps of cis-regulatory elements and single-cell transcriptomes, we construct the regulatory network of early development, which helps to identify the key modulators for lineage specification. Finally, we find that the activities of cis-regulatory elements and their associated open chromatin diminished before major ZGA. Surprisingly, we observed many loci showing non-canonical, large open chromatin domains over the entire transcribed units in minor ZGA, supporting the presence of an unusually permissive chromatin state. Together, these data reveal a unique spatiotemporal chromatin configuration that accompanies early mammalian development. Mouse preimplantation embryos were obtained from crosses of C57BL/6N and DBA/2N. ATAC-seq was performed in these embryos at various stages in preimplantation development.
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Project description:Mammalian preimplantation development is a complex process involving dramatic changes in the transcriptional architecture. Through single-cell RNA-sequencing (RNA-seq), we report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos. Based on single nucleotide variants (SNVs) in blastomere mRNAs and paternal-specific SNPs, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25-53%). By weighted gene co-expression network analysis (WGCNA), we find that each developmental stage can be concisely delineated by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation, and metabolism in a step-wise fashion from cleavage to morula. Cross-species comparisons reveal that the majority of human stage-specific modules (7 out of 9) are remarkably preserved, only to diverge in developmental specificity and timing in mice. We further identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely key players in driving mammalian preimplantation development. Collectively, we demonstrate that mammalian preimplantation development is orchestrated by evolutionarily conserved genetic programs that diverge in developmental timing. Our results provide a valuable resource to dissect gene regulatory mechanism underlying progressive development of early mammalian embryos.
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