Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1006851 | ENA |
REPOSITORIES: ENA
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Project description:Translational regulation plays a critical role during oocyte-to-embryo transition including zygotic genome activation. However, the translatome during OET and molecular mechanisms underlying human ZGA remain largely uncharted. Here, we integrated ultra-low-input Ribo-seq with RNA-seq (R2-lite) to jointly profile the translatome and transcriptome from the same samples across 8 stages in human oocytes and early embryos. These data not only unveil conservation and divergence of the translation landscapes between human and mouse OET, but also identify critical regulators of human ZGA.
2022-10-08 | GSE197265 | GEO
Project description:Oocyte maturation is vital to attain full competence required fertilization and embryogenesis. As a maternal effect factor, NLRP14 is preferentially expressed in mammalian oocytes and early embryos. Yet the role and molecular mechanism of NLRP14 in oocyte maturation and early embryogenesis is largely unknown. Whether NLRP14 deficiency accounts for human infertility with oocyte and embryo defects remains to be elucidated. Here, NLRP14 is identified essential for establishment of competent oocytes that can sustain early embryo development. Maternal deficiency of Nlrp14 results in sterility characterized by oocyte maturation defects and early embryo arrest. Nlrp14 ablation leads to compromised oocyte quality and developmental competence due to impaired oocyte cytoplasmic and nuclear maturation. Mechanistically, NLRP14 interacts with UHRF1 in oocyte cytoplasm to protect it from proteasome-dependent degradation, and perturbs maternal mRNA zygotic-decay and zygotic genome activation during maternal-zygotic transition. Furthermore, compound heterozygous pathogenic variants in NLRP14 gene are identified in infertile women with early embryonic arrest, which interrupt the NLRP14-UHRF1 interaction or UHRF1 protein expression. Our data uncover a vital role of NLRP14 as a new cytoplasmic-specific modulator of UHRF1 in oocyte meiotic maturation and early embryogenesis, which should provide new insights into risk prediction and genetic diagnosis for female infertility.
2024-06-01 | GSE234001 | GEO
Project description:Maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment of oocyte transits to the zygotic genome driven expression program, and terminally differentiated oocyte and sperm are reprogrammed to totipotency. Metaphase II (MII) oocytes and zygotes (one-cell embryo) serve as the mature oocyte and the initiation of pre-implantation embryo development respectively, and characterizing their molecular landscapes at protein levels plays an important role in uncovering MZT and zygotic genome activation (ZGA )in mammals. Here we used an ultrasensitive proteomic approach to depict an in-depth landscape for the very early stage of mouse MZT.
2023-05-23 | PXD041399 | Pride
Project description:Dynamic epigenomic reprogramming occurs during mammalian oocyte maturation and early development. However, the underlying transcription circuitry remains poorly characterized. By mapping cis-regulatory elements using H3K27ac, we identified putative enhancers in mouse oocytes and early embryos distinct from those in adult tissues, enabling global transitions of regulatory landscapes around fertilization and implantation. Gene deserts harbor prevalent putative enhancers in fully-grown oocytes linked to oocyte-specific gene and repeat activation. Embryo-specific enhancers are primed prior to zygotic genome activation and are restricted by oocyte-inherited H3K27me3. Putative enhancers in oocytes often manifest H3K4me3, bidirectional transcription, Pol II binding, and can drive transcription in STARR-seq and a reporter assay. Finally, motif analysis of these elements identified crucial regulators of oogenesis – TCF3 and TCF12, the deficiency of which impairs activation of key oocyte genes and folliculogenesis. These data reveal distinctive regulatory landscapes and their interacting TFs that underpin the development of mammalian oocytes and early embryos.
2024-03-23 | GSE217970 | GEO
Project description:In mammals, meiotically competent oocytes develop cyclically during ovarian folliculogenesis. During their development, prophase I arrested oocytes are highly transcriptionally active in preparation for the resumption of meiosis and early stages of embryogenesis prior to the maternal to zygotic transition. Defective oocyte development during folliculogenesis leads to meiotic defects, aneuploidy, follicular atresia, or non-viable embryos. SUMOylation, a dynamic post-translational protein modification, is essential for oocyte development during folliculogenesis and to regulate meiotic maturation in mice. We generated a novel oocyte-specific knockout of Ube2i, the sole SUMO E2 ligase, to test its role growing ovarian follicles using Zp3-cre. Ube2i Zp3-cre+ female mice are sterile with oocytes with defects in meiotic progression but not meiotic resumption. Importantly, fully grown oocytes do not silence transcription and prematurely activate the zygotic transcriptional program. This work uncovers unknown functions of UBE2i as a key orchestrator of chromatin and transcriptional regulation in oocytes.
2023-08-23 | GSE218484 | GEO
Project description:The oocyte-to-embryo transition converts terminally differentiated gametes into a totipotent embryo. Fertilized embryos undergo the resetting of the transcriptional program as the zygotic genome is activated from a silenced state started from the late-stage oocyte. How transcriptome, translatome, and proteome interplay in this critical developmental window remains poorly understood. Utilizing a highly sensitive mass spectrometry, we obtained high-quality proteome landscapes including nearly 6,000 genes spanning 10 stages, from the mouse full-grown oocyte (FGO) to blastocyst, using 100 oocytes/embryos at each stage. By integrative analysis with corresponding transcriptomes and translatomes, we found transcription and translation levels can not reflect protein abundance in most cases. From FGOs to the 4-cell embryos, the proteomes are predominated by FGO-produced proteins, while the transcriptome and the translatome are much more dynamic. FGO-originated proteins frequently persist in embryos after the corresponding transcripts are already downregulated or decayed. Improved concordance between protein and RNA is observed for genes starting translation only upon meiotic resumption or transcribed only in embryos, although the detected protein dynamics often lag behind transcription and translation. Concordance between protein and transcription/translation is associated with protein half-lives. Finally, a kinetic model well predicts protein dynamics when incorporating both the initial protein abundance in FGO and translation kinetics across developmental stages. In sum, our study reveals multilayer control of gene expression during oocyte maturation and embryogenesis.
2023-06-27 | PXD035696 | Pride
Project description:As an important post-transcriptional regulatory mechanism, asymmetric localization of mRNAs is essential for cell polarity and cell fate determination during early development. In an effort to understand localization of mRNAs encoding proteasome components during Xenopus oocyte-to-embryo transition, we discovered that the endoplasmic reticulum (ER), which is thought to mainly serve “house-keeping” roles in the cell, plays a multifaceted role in controlling localization of maternal RNAs. Our RNA-seq analysis of fractionated transcripts reveals that more than 40% of RNAs, including proteasome mRNAs, are present on the ER in Xenopus oocytes. After meiotic maturation, a large fraction of ER-associated RNA is released into the cytosol. The release of proteasome RNAs from the ER into the cytosol is conserved during mouse oocyte maturation. Our comparative proteomic analysis and ribonucleoprotein immunoprecipitation demonstrate that the majority of ER-associated RNA-binding proteins (RBPs) remain associated with the ER after oocyte maturation. However, all ER-associated RBPs analyzed exhibit reduced binding to some of their target RNAs after oocyte maturation, providing a mechanistic explanation for the dynamic regulation of RNA-ER association. We further show that the ER is remodeled massively during Xenopus oocyte maturation, leading to the formation of a widespread tubular ER network in the animal hemisphere that is required for the asymmetric localization of proteasome mRNAs in mature eggs. To our knowledge, our findings demonstrate for the first time that dynamic regulation of RNA-ER association and remodeling of the ER are fundamentally important for asymmetric localization of RNAs during development.
2022-12-15 | PXD033018 | Pride
Project description:In most species, early germline development occurs in the absence of transcription with germline determinants subject to complex translational and post-translational regulations. Here, we report for the first time that early germline development is influenced by dynamic regulation of the proteasome system, previously thought to be ubiquitously expressed and to serve ‘housekeeping’ roles in controlling protein homeostasis. We show that proteasomes are present in a gradient with highest levels in the animal hemisphere but extending into the vegetal hemisphere of Xenopus oocytes. This distribution changes dramatically during the oocyte-to-embryo transition, with proteasomes becoming enriched in and restricted to the animal hemisphere and therefore separated from vegetally localized germline determinants. We identify Dead-end1 (Dnd1), a master regulator of vertebrate germline development, as a novel substrate of the ubiquitin-independent proteasomes. In the oocyte, ubiquitin-independent proteasomal degradation acts together with translational repression to prevent premature accumulation of Dnd1 protein. In the embryo, artificially increasing ubiquitin-independent proteasomal degradation in the vegetal pole interferes with germline development. Our work thus reveals novel inhibitory functions and spatial regulation of the ubiquitin-independent proteasome during vertebrate germline development.
2019-04-10 | PXD013446 | Pride
Project description:We profiled transcriptomes from Cnot6l deadenylase knock-out mouse GV oocytes, MII eggs and 1-cell zygotes in order to analyse its function during the oocyte-to-embryo (OET) transition. Transcriptome of wild-type golden hamster GV oocytes was also profiled.
2018-07-10 | GSE116771 | GEO
Project description:Oocyte quality largely determines the embryo development after fertilization. High-quality oocyte requires the competence of both cytoplasm and nucleus. However, clinically, the treatment of developmentally competent oocytes was limited. Here, in order to improve the embryo development efficiency of developmentally incompetent oocytes, we performed spindle-chromosome complex (SCC) transfer between in vitro matured (IVM) and in vivo matured (IVO) oocytes of the non-human primate. We observed that the blastocyst rate of embryos derived by transferring the SCC of IVM (IVM-SCC) oocytes into enucleated IVO oocytes was comparable with that of embryos derived by IVO oocytes. After transferring the reconstructed embryos into the uterus of surrogate mothers, two live rhesus monkeys were obtained, indicating that the nuclei of IVM oocytes support both the pre-and post-implantation embryo development of non-human primates.
2023-07-15 | GSE233232 | GEO