bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2024‒10‒13
ten papers selected by
Gabriele Zaffagnini, Centre for Genomic Regulation
  1. RNA surveillance by the RNA helicase MTR4 determines volume of mouse oocytes.
  2. Cryo-EM structure of the human subcortical maternal complex and the associated discovery of infertility-associated variants.
  3. Genetic interaction mapping of Aurora protein kinases in mouse oocytes.
  4. A role for BYN-1/bystin in cellular uptake and clearance of residual bodies in the Caenorhabditis elegans germline.
  5. Genome folding and zygotic genome activation in mammalian preimplantation embryos.
  6. SMARTdb: An Integrated Database for Exploring Single-cell Multi-omics Data of Reproductive Medicine.
  7. Single-nucleus multiomics reveals the gene-regulatory networks underlying sex determination of murine primordial germ cells.
  8. A germline-to-soma signal triggers an age-related decline of mitochondrial stress response.
  9. A spotlight on factors influencing the in vitro folliculogenesis of isolated preantral follicles.
  10. HSP70 inhibits CHIP E3 ligase activity to maintain germline function in Caenorhabditis elegans.
  1. Dev Cell. 2024 Oct 04. pii: S1534-5807(24)00537-9. [Epub ahead of print]
    RNA surveillance by the RNA helicase MTR4 determines volume of mouse oocytes.
    Yun-Wen Wu, Zuo-Qi Deng, Yan Rong, Guo-Wei Bu, Yu-Ke Wu, Xuan Wu, Hong Cheng, Heng-Yu Fan.
      Oocytes are the largest cell type in multicellular animals. Here, we show that mRNA transporter 4 (MTR4) is indispensable for oocyte growth and functions as part of the RNA surveillance mechanism, which is responsible for nuclear waste RNA clearance. MTR4 ensures the normal post-transcriptional processing of maternal RNAs, their nuclear export to the cytoplasm, and the accumulation of properly processed transcripts. Oocytes with Mtr4 knockout fail to accumulate sufficient and normal transcripts in the cytoplasm and cannot grow to normal sizes. MTR4-dependent RNA surveillance has a previously unrecognized function in maintaining a stable nuclear environment for the establishment of non-canonical histone H3 lysine-4 trimethylation and chromatin reorganization, which is necessary to form a nucleolus-like structure in oocytes. In conclusion, MTR4-dependent RNA surveillance activity is a checkpoint that allows oocytes to grow to a normal size, undergo nuclear and cytoplasmic maturation, and acquire developmental competence.
    Keywords:  RNA exosome; RNA surveillance; chromatin configuration; germ cell; histone modification; post-transcriptional regulation
    DOI:  https://doi.org/10.1016/j.devcel.2024.09.009
  2. Nat Struct Mol Biol. 2024 Oct 08.
    Cryo-EM structure of the human subcortical maternal complex and the associated discovery of infertility-associated variants.
    Pengliang Chi, Guojin Ou, Sibei Liu, Qianhong Ma, Yuechao Lu, Jinhong Li, Jialu Li, Qianqian Qi, Zhuo Han, Zihan Zhang, Qingting Liu, Li Guo, Jing Chen, Xiang Wang, Wei Huang, Lei Li, Dong Deng.
      The functionally conserved subcortical maternal complex (SCMC) is essential for early embryonic development in mammals. Reproductive disorders caused by pathogenic variants in NLRP5, TLE6 and OOEP, three core components of the SCMC, have attracted much attention over the past several years. Evaluating the pathogenicity of a missense variant in the SCMC is limited by the lack of information on its structure, although we recently solved the structure of the mouse SCMC and proposed that reproductive disorders caused by pathogenic variants are related to the destabilization of the SCMC core complex. Here we report the cryogenic electron microscopy structure of the human SCMC and uncover that the pyrin domain of NLRP5 is essential for the stability of SCMC. By combining prediction of SCMC stability and in vitro reconstitution, we provide a method for identifying deleterious variants, and we successfully identify a new pathogenic variant of TLE6 (p.A396T). Thus, on the basis of the structure of the human SCMC, we offer a strategy for the diagnosis of reproductive disorders and the discovery of new infertility-associated variants.
    DOI:  https://doi.org/10.1038/s41594-024-01396-2
  3. Front Cell Dev Biol. 2024 ;12 1455280
    Genetic interaction mapping of Aurora protein kinases in mouse oocytes.
    Cecilia S Blengini, Karen Schindler.
      The Aurora Kinases (AURKs) are a family of serine-threonine protein kinases critical for cell division. Somatic cells express only AURKA and AURKB. However, mammalian germ cells and some cancer cells express all three isoforms. A major question in the field has been determining the molecular and cellular changes when cells express three instead of two aurora kinases. Using a systematic genetic approach involving different Aurora kinase oocyte-specific knockout combinations, we completed an oocyte-AURK genetic interaction map and show that one genomic copy of Aurka is necessary and sufficient to support female fertility and oocyte meiosis. We further confirm that AURKB and AURKC alone cannot compensate for AURKA. These results highlight the importance of AURKA in mouse oocytes, demonstrating that it is required for spindle formation and proper chromosome segregation. Surprisingly, a percentage of oocytes that lack AURKB can complete meiosis I, but the quality of those eggs is compromised, suggesting a role in AURKB to regulate spindle assembly checkpoint or control the cell cycle. Together with our previous studies, we wholly define the genetic interplay among the Aurora kinases and reinforce the importance of AURKA expression in oocyte meiosis.
    Keywords:  aneuploidy; aurora kinase; meiosis; mouse model; oocyte
    DOI:  https://doi.org/10.3389/fcell.2024.1455280
  4. Development. 2024 Oct 01. pii: dev202694. [Epub ahead of print]151(19):
    A role for BYN-1/bystin in cellular uptake and clearance of residual bodies in the Caenorhabditis elegans germline.
    Hyemin Min, Emily L Spaulding, Catherine S Sharp, Pankaj Garg, Esther Jeon, Lyn S Miranda Portillo, Noah A Lind, Dustin L Updike.
      GLH/Vasa/DDX4 helicases are core germ-granule proteins that promote germline development and fertility. A yeast-two-hybrid screen using Caenorhabditis elegans GLH-1 as bait identified BYN-1, the homolog of human bystin/BYSL. In humans, bystin promotes cell adhesion and invasion in gliomas, and, with its binding partner trophinin, triggers embryonic implantation into the uterine wall. C. elegans embryos do not implant and lack a homolog of trophinin, but both trophinin and GLH-1 contain unique decapeptide phenylalanine-glycine (FG)-repeat domains. In germ cells, we find endogenous BYN-1 in the nucleolus, partitioned away from cytoplasmic germ granules. However, BYN-1 enters the cytoplasm during spermatogenesis to colocalize with GLH-1. Both proteins become deposited in residual bodies (RBs), which are then engulfed and cleared by the somatic gonad. We show that BYN-1 acts upstream of CED-1 to drive RB engulfment, and that removal of the FG-repeat domains from GLH-1 and GLH-2 can partially phenocopy byn-1 defects in RB clearance. These results point to an evolutionarily conserved pathway whereby cellular uptake is triggered by the cytoplasmic mobilization of bystin/BYN-1 to interact with proteins harboring FG-repeats.
    Keywords:  BYN-1; Bystin; FG-repeat; GLH-1; Residual bodies; Trophinin
    DOI:  https://doi.org/10.1242/dev.202694
  5. Curr Opin Genet Dev. 2024 Oct 08. pii: S0959-437X(24)00117-5. [Epub ahead of print]89 102268
    Genome folding and zygotic genome activation in mammalian preimplantation embryos.
    Anastasiia Bondarieva, Kikuë Tachibana.
      The totipotent one-cell embryo, or zygote, gives rise to all germ layers and extraembryonic tissues that culminate in the development of a new organism. A zygote is produced at fertilisation by the fusion of differentiated germ cells, egg and sperm. The chromatin of parental genomes is reprogrammed and spatially reorganised in the early embryo. The 3D chromatin organisation is established de novo after fertilisation by a cohesin-dependent mechanism of loop extrusion that forms chromatin loops and topologically associating domains (TADs). Strengthening of TAD insulation is concomitant with the transcriptional 'awakening' of the embryo known as zygotic genome activation (ZGA). Whether and how these processes are causally linked remains poorly understood. In this review, we discuss recent findings of 3D chromatin organisation in mammalian gametes and embryos and how these are potentially related to ZGA.
    DOI:  https://doi.org/10.1016/j.gde.2024.102268
  6. Genomics Proteomics Bioinformatics. 2024 Sep 13. pii: qzae005. [Epub ahead of print]22(3):
    SMARTdb: An Integrated Database for Exploring Single-cell Multi-omics Data of Reproductive Medicine.
    Zekai Liu, Zhen Yuan, Yunlei Guo, Ruilin Wang, Yusheng Guan, Zhanglian Wang, Yunan Chen, Tianlu Wang, Meining Jiang, Shuhui Bian.
      Single-cell multi-omics sequencing has greatly accelerated reproductive research in recent years, and the data are continually growing. However, utilizing these data resources is challenging for wet-lab researchers. A comprehensive platform for exploring single-cell multi-omics data related to reproduction is urgently needed. Here, we introduce the single-cell multi-omics atlas of reproduction (SMARTdb), an integrative and user-friendly platform for exploring molecular dynamics of reproductive development, aging, and disease, which covers multi-omics, multi-species, and multi-stage data. We curated and analyzed single-cell transcriptomic and epigenomic data of over 2.0 million cells from 6 species across the entire lifespan. A series of powerful functionalities are provided, such as "Query gene expression", "DIY expression plot", "DNA methylation plot", and "Epigenome browser". With SMARTdb, we found that the male germ cell-specific expression pattern of RPL39L and RPL10L is conserved between human and other model animals. Moreover, DNA hypomethylation and open chromatin may collectively regulate the specific expression pattern of RPL39L in both male and female germ cells. In summary, SMARTdb is a powerful platform for convenient data mining and gaining novel insights into reproductive development, aging, and disease. SMARTdb is publicly available at https://smart-db.cn.
    Keywords:  Database; Embryo; Germ cell; Gonad; Single-cell multi-omics
    DOI:  https://doi.org/10.1093/gpbjnl/qzae005
  7. bioRxiv. 2024 Sep 25. pii: 2024.02.19.581036. [Epub ahead of print]
    Single-nucleus multiomics reveals the gene-regulatory networks underlying sex determination of murine primordial germ cells.
    Adriana K Alexander, Karina F Rodriguez, Yu-Ying Chen, Ciro M Amato, Martin A Estermann, Barbara Nicol, Xin Xu, Humphrey Hung-Chang Yao.
      Accurate specification of female and male germ cells during embryonic development is critical for sexual reproduction. Primordial germ cells (PGCs) are the bipotential precursors of mature gametes that commit to an oogenic or spermatogenic fate in response to sex-determining cues from the fetal gonad. The critical processes required for PGCs to integrate and respond to signals from the somatic environment in gonads are not understood. In this study, we developed the first single-nucleus multiomics map of chromatin accessibility and gene expression during murine PGC development in both XX and XY embryos. Profiling of cell-type specific transcriptomes and regions of open chromatin from the same cell captured the molecular signatures and gene networks underlying PGC sex determination. Joint RNA and ATAC data for single PGCs resolved previously unreported PGC subpopulations and cataloged a multimodal reference atlas of differentiating PGC clusters. We discovered that regulatory element accessibility precedes gene expression during PGC development, suggesting that changes in chromatin accessibility may prime PGC lineage commitment prior to differentiation. Similarly, we found that sexual dimorphism in chromatin accessibility and gene expression increased temporally in PGCs. Combining single-nucleus sequencing data, we computationally mapped the cohort of transcription factors that regulate the expression of sexually dimorphic genes in PGCs. For example, the gene regulatory networks of XX PGCs are enriched for the transcription factors, TFAP2c, TCFL5, GATA2, MGA, NR6A1, TBX4, and ZFX. Sex-specific enrichment of the forkhead-box and POU6 families of transcription factors was also observed in XY PGCs. Finally, we determined the temporal expression patterns of WNT, BMP, and RA signaling during PGC sex determination, and our discovery analyses identified potentially new cell communication pathways between supporting cells and PGCs. Our results illustrate the diversity of factors involved in programming PGCs towards a sex-specific fate.
    DOI:  https://doi.org/10.1101/2024.02.19.581036
  8. Nat Commun. 2024 Oct 08. 15(1): 8723
    A germline-to-soma signal triggers an age-related decline of mitochondrial stress response.
    Liankui Zhou, Liu Jiang, Lan Li, Chengchuan Ma, Peixue Xia, Wanqiu Ding, Ying Liu.
      The abilities of an organism to cope with extrinsic stresses and activate cellular stress responses decline during aging. The signals that modulate stress responses in aged animals remain to be elucidated. Here, we discover that feeding Caenorhabditis elegans (C. elegans) embryo lysates to adult worms enabled the animals to activate the mitochondrial unfolded protein response (UPRmt) upon mitochondrial perturbations. This discovery led to subsequent investigations that unveil a hedgehog-like signal that is transmitted from the germline to the soma in adults to inhibit UPRmt in somatic tissues. Additionally, we find that the levels of germline-expressed piRNAs in adult animals markedly decreased. This reduction in piRNA levels coincides with the production and secretion of a hedgehog-like signal and suppression of the UPRmt in somatic cells. Building upon existing research, our study further elucidates the intricate mechanisms of germline-to-soma signaling and its role in modulating the trade-offs between reproduction and somatic maintenance within the context of organismal aging.
    DOI:  https://doi.org/10.1038/s41467-024-53064-0
  9. J Assist Reprod Genet. 2024 Oct 07.
    A spotlight on factors influencing the in vitro folliculogenesis of isolated preantral follicles.
    Pritha Dey, Noemi Monferini, Ludovica Donadini, Valentina Lodde, Federica Franciosi, Alberto Maria Luciano.
      Female fertility preservation via complete in vitro folliculogenesis is still chimerical. Due to many factors affecting the efficiency of isolation and culture of preantral follicles, the improvement of techniques geared to fertility preservation in higher mammals seems to be at an impasse. We need an objective view of the current stand to understand how to progress further. As such, a survey was conducted to analyze the relative distribution of studies performed in ten mammalian species on preantral follicle culture available on PubMed. Using the bovine as a reference model, we explore some factors influencing data variation that contribute to the difficulty in reproducing studies. While years of research have enabled the recapitulation of folliculogenesis from as modest as the early antral follicle stage ex vivo, in vitro preantral folliculogenesis remains elusive. Herein, we revisit the classical evidence that laid the foundations for understanding preantral folliculogenesis and review the length, breadth, and depth of information that the era of big data has currently levied. Moving forward, we recognize the urgency of synthesizing the multi-disciplinary approaches to mimic folliculogenesis in vitro to achieve a translational landscape of infertility at individual and large-scale conservation levels.
    Keywords:  Bovine; Fertility preservation; Follicle culture; Follicle isolation; Folliculogenesis; Ovarian aging; Ovarian reserve; Ovary; Preantral follicle; Primordial follicle
    DOI:  https://doi.org/10.1007/s10815-024-03277-5
  10. J Biol Chem. 2024 Oct 07. pii: S0021-9258(24)02366-4. [Epub ahead of print] 107864
    HSP70 inhibits CHIP E3 ligase activity to maintain germline function in Caenorhabditis elegans.
    Pankaj Thapa, Rupesh V Chikale, Natalia A Szulc, Maria-Teodora Pandrea, Agnieszka Sztyler, Khushboo Jaggi, Marta Niklewicz, Remigiusz A Serwa, Thorsten Hoppe, Wojciech Pokrzywa.
      The ubiquitin-proteasome system is crucial for proteostasis, particularly during proteotoxic stress. The interaction between heat shock protein 70 (HSP70) and the ubiquitin ligase CHIP plays a key role in this process. Our study investigates the C. elegans orthologs HSP-1 and CHN-1, demonstrating that HSP-1 binding decreases CHN-1 E3 ligase activity, aligning with the inhibitory effects observed in human HSP70-CHIP interactions. To explore the physiological significance of this inhibition, we utilized the HSP-1EEYD mutant, which binds CHN-1 without reducing its activity, expressed in C. elegans. Our results reveal that the HSP-1-CHN-1 interaction is critical for maintaining germline integrity under heat stress by preventing excessive turnover of essential reproductive proteins. In HSP-1EEYD nematodes, this protective mechanism is impaired, leading to disrupted stress-induced apoptosis, which is restored by CHN-1 depletion. Additionally, proteomic analysis identified DAF-18/PTEN as a potential CHN-1 substrate, which becomes destabilized when CHN-1 activity is not downregulated by HSP-1 during stress. Depleting DAF-18 significantly compromises the reproductive benefits observed from CHN-1 knockout in HSP-1EEYD mutants, suggesting that the maintenance of DAF-18 plays a role in the observed phenotypes. These findings highlight the importance of HSP-1 in regulating CHN-1 E3 ligase activity to preserve germline function under stress conditions.
    DOI:  https://doi.org/10.1016/j.jbc.2024.107864
This page is being maintained by Thomas Krichel. It was last updated on 2024‒10‒13 at 8:17.