Single-cell transcriptomics of human oocytes: environment-driven metabolic competition and compensatory mechanisms during oocyte maturation
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ABSTRACT:
PROVIDER: PRJNA434577 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6748700_1.fastq.gz | Fastqsanger.gz | |||
| SRR6748700_2.fastq.gz | Fastqsanger.gz | |||
| SRR6748701_1.fastq.gz | Fastqsanger.gz | |||
| SRR6748701_2.fastq.gz | Fastqsanger.gz | |||
| SRR6748702_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Aim: The mechanisms coordinating maturation with an environment-driven metabolic shift, a critical step in determining the developmental potential of human in vitro matured (IVM) oocytes, remains to be elucidated. Here, we explored the key genes regulating human oocyte maturation using single-cell RNA sequencing and illuminated the compensatory mechanism from a metabolic perspective by analyzing gene expression. Results: Three key genes that encode CoA-related enzymes were screened from the RNA sequencing data. Two of them, ACAT1 and HADHA, were closely related to the regulation of substrate production in the Krebs cycle. Dysfunction of the Krebs cycle was induced by decreases in the activity of specific enzymes. Further, the activator of these enzymes, the calcium concentration, was also decreased because of the failure of influx of exogenous calcium. Although release of endogenous calcium from the endoplasmic reticulum and mitochondria met the requirement for maturation, excessive release resulted in aneuploidy and developmental incompetence. High nicotinamide nucleotide transhydrogenase expression induced NADPH dehydrogenation to compensate for the NADH shortage resulting from the dysfunction of the Krebs cycle. Importantly, high NADP+ levels activated DPYD to enhance the repair of DNA double-strand breaks to maintain euploidy. Innovation: The present study shows for the first time that exposure to the in vitro environment can lead to the decline of energy metabolism in human oocytes during maturation but that a compensatory action maintains their developmental competence. Conclusions: In vitro maturation of human oocytes is mediated through a cascade of competing and compensatory actions driven by genes encoding enzymes.
2018-04-10 | GSE110798 | GEO
Project description:AimsThe mechanisms coordinating maturation with an environment-driven metabolic shift, a critical step in determining the developmental potential of human in vitro maturation (IVM) oocytes, remain to be elucidated. Here we explored the key genes regulating human oocyte maturation using single-cell RNA sequencing and illuminated the compensatory mechanism from a metabolic perspective by analyzing gene expression.ResultsThree key genes that encode CoA-related enzymes were screened from the RNA sequencing data. Two of them, ACAT1 and HADHA, were closely related to the regulation of substrate production in the Krebs cycle. Dysfunction of the Krebs cycle was induced by decreases in the activity of specific enzymes. Furthermore, the activator of these enzymes, the calcium concentration, was also decreased because of the failure of influx of exogenous calcium. Although release of endogenous calcium from the endoplasmic reticulum and mitochondria met the requirement for maturation, excessive release resulted in aneuploidy and developmental incompetence. High nicotinamide nucleotide transhydrogenase expression induced NADPH dehydrogenation to compensate for the NADH shortage resulting from the dysfunction of the Krebs cycle. Importantly, high NADP+ levels activated DPYD to enhance the repair of DNA double-strand breaks to maintain euploidy.InnovationThe present study shows for the first time that exposure to the in vitro environment can lead to the decline of energy metabolism in human oocytes during maturation but that a compensatory action maintains their developmental competence.ConclusionIn vitro maturation of human oocytes is mediated through a cascade of competing and compensatory actions driven by genes encoding enzymes.
| S-EPMC6338670 | biostudies-literature
Project description:In this study, we applied 1D SDS-PAGE and RP-LC-MS/MS to investigate the proteins stored in GV mouse oocytes. This high-performance strategy allowed us to define a set of 1405 different mouse GV oocyte proteins. It is confirmed that this study will help us to understand the diverse biological processes occurring in mouse oocytes and during early embryo development. However, compared with proteomic analysis of other cells and tissues, such as embryonic stems from cells and liver, the proteins identified in mature mouse oocytes were limited. This was mainly due to the fact that oocytes obtained from each mouse were very limited. We believe that the catalog of maternal proteins presented in this article is a starting point and we anticipate that more researches on the oocyte proteome will deduce most of the maternal proteins.
2020-09-17 | PXD014314 | Pride
Project description:In this study we investigated the protein expression patterns during human oocyte in vitro and in vivo maturation (IVO) by single-cell quantitative proteomic analysis of 36 human oocytes. Among 2,094 proteins quantified in 34 oocytes (GV: 11 oocytes, IVM: 12 oocytes, IVO: 11 oocytes), 224 were differential between IVO and GV oocytes during in vivo maturation, and 61 between IVM and IVO oocytes.
2022-08-02 | PXD023366 | Pride
Project description:The genetic causes of oocyte meiotic deficiency (OMD), a form of primary infertility characterised by the production of immature oocytes, remain largely unexplored. Using whole exome sequencing, we found that 26% of a cohort of 23 subjects with OMD harboured the same homozygous nonsense pathogenic mutation in PATL2, a gene encoding a putative RNA-binding protein. Using Patl2 knockout mice, we confirmed that PATL2 deficiency disturbs oocyte maturation, since oocytes and zygotes exhibit morphological and developmental defects respectively. PATL2's amphibian orthologue is involved in the regulation of oocyte mRNA as a partner of CPEB. However, Patl2's expression profile throughout oocyte development in mice, alongside colocalisation experiments with Cpeb1, Msy2 and Ddx6 (three oocyte RNA-regulators) suggest an original role for Patl2 in Mammals. Accordingly, transcriptomic analysis of oocytes from WT and Patl2-/- animals demonstrated that in the absence of Patl2, expression levels of a select number of highly relevant genes involved in oocyte maturation and early embryonic development are deregulated. In conclusion, PATL2 is a novel actor of mammalian oocyte maturation whose invalidation causes OMD in humans.
| EGAS00001002903 | EGA
Project description:In vitro oocyte maturation (IVM) holds great promise as a tool for enhancing clinical treatment of infertility, enhancing availability of non human primates for development of disease models, and facilitating endangered species preservation. However, IVM outcomes have remained significantly below success rates obtained using in vivo matured (VVM) oocytes from humans and non human primates. A cDNA array based analysis is presented, comparing the transcriptomes of VVM oocytes with IVM oocytes. We observe a small set of just 59 mRNAs that are differentially expressed between the two cell types. These mRNAs are related to cellular homeostasis, cell-cell interactions including growth factor and hormone stimulation and cell adhesion, and other functions such as mRNA stability and translation. Additionally, we observe in IVM oocytes overexpression of PLAGL1 and MEST, two maternally imprinted genes, indicating a possible interruption or loss of correct epigenetic programming. These results indicate that, under certain IVM conditions, oocytes that are molecularly highly similar to VVM oocytes can be obtained, however the interruption of normal oocyte-somatic cell interactions during the final hours of oocyte maturation may preclude the establishment of full developmental competence. Keywords: oocyte maturation Comparison of in vitro matured MII-stage oocytes (4 biological replicates) with in vivo matured MII-stage oocytes (4 biological replicates)
2009-05-20 | E-GEOD-11895 | biostudies-arrayexpress
Project description:There is massive destruction of transcripts during maturation of mouse oocytes. The objective of this project was to identify and characterize the transcripts that are degraded versus those that are stable during the transcriptionally silent germinal vesicle (GV)-stage to metaphase II (MII)-stage transition using the microarray approach. A system for oocyte transcript amplification using both internal and 3'-poly(A) priming was utilized to minimize the impact of complex variations in transcript polyadenylation prevalent during this transition. Transcripts were identified and quantified using Affymetrix Mouse Genome 430 v2.0 GeneChip. The significantly changed and stable transcripts were analyzed using Ingenuity Pathways Analysis and GenMAPP/MAPPFinder to characterize the biological themes underlying global changes in oocyte transcripts during maturation. It was concluded that the destruction of transcripts during the GV to MII transition is a selective rather than promiscuous process in mouse oocytes. In general, transcripts involved in processes that are associated with meiotic arrest at the GV-stage and the progression of oocyte maturation, such as oxidative phosphorylation, energy production, and protein synthesis and metabolism, were dramatically degraded. In contrast, transcripts encoding participants in signaling pathways essential for maintaining the unique characteristics of the MII-arrested oocyte, such as those involved in protein kinase pathways, were the most prominent among those stables. Experiment Overall Design: Comparison immature GV-stage oocyte (3 biological replicates) with mature MII-stage oocytes (3 biological replicates)
2007-11-13 | E-GEOD-5668 | biostudies-arrayexpress
Project description:We discovered that mouse oocytes contain novel non-membrane-bound organelles, which we named EndoLysosomal Vesicular Assemblies (ELVAs). ELVAs contain endolysosomal and autophagy vesicles, as well as proteasomes. In immature oocytes, ELVAs store ubiquitinated proteins and show little degradative activity. During oocyte maturation, ELVAs increase protein degradation, thereby degrading the stored proteins. To understand which proteins are being degraded inside ELVAs during oocyte maturation we treated mouse oocytes with or without the lysosomal inhibitor Bafilomycin A1 (BafA1) during maturation and subjected equal number of in vitro matured oocytes to mass spec, looking for enriched proteins in the BafA1-treated sample.
2024-02-20 | PXD042769 | Pride
Project description:In vitro oocyte maturation (IVM) holds great promise as a tool for enhancing clinical treatment of infertility, enhancing availability of non human primates for development of disease models, and facilitating endangered species preservation. However, IVM outcomes have remained significantly below success rates obtained using in vivo matured (VVM) oocytes from humans and non human primates. A cDNA array based analysis is presented, comparing the transcriptomes of VVM oocytes with IVM oocytes. We observe a small set of just 59 mRNAs that are differentially expressed between the two cell types. These mRNAs are related to cellular homeostasis, cell-cell interactions including growth factor and hormone stimulation and cell adhesion, and other functions such as mRNA stability and translation. Additionally, we observe in IVM oocytes overexpression of PLAGL1 and MEST, two maternally imprinted genes, indicating a possible interruption or loss of correct epigenetic programming. These results indicate that, under certain IVM conditions, oocytes that are molecularly highly similar to VVM oocytes can be obtained, however the interruption of normal oocyte-somatic cell interactions during the final hours of oocyte maturation may preclude the establishment of full developmental competence. Keywords: oocyte maturation
2009-05-20 | GSE11895 | GEO
Project description:The transition from a transcriptionally active state (GV) to a transcriptionally inactive state (mature MII oocytes) is one of the requirements for the acquisition of oocyte developmental competence. After maturation, oocytes are mostly transcriptionally quiescent, and developmental competence prior to embryonic genome activation (EGA) relies on maternal RNA and proteins. The landscape of expressed genes at the MII stage could be mostly driven by post-transcriptional mechanisms, such as alternative splicing (AS). With the development of single cell transcriptome analysis, genome wide AS analysis becomes technically feasible and available to fully characterize the AS patterns in human oocytes. Profiling spliced mRNA isoforms might provide novel information on the molecular mechanisms driving early development, and might be a source of potential biomarkers of oocyte quality. The goal of the present study is to perform a transcriptomic analysis in oocytes at different stages of maturation, to identify the profiles of alternative spliced isoforms produced in both oocyte’ stages.
2020-06-16 | GSE152525 | GEO