bims-mazytr Biomed News
on Maternal‐to‐zygotic transition
Issue of 2025–04–27
six papers selected by
川一刀
  1. RIF1 controls replication timing in early mouse embryos independently of lamina-associated nuclear organization.
  2. Deciphering Sequence Determinants of Zygotic Genome Activation Genes: Insights From Machine Learning and the ZGAExplorer Platform.
  3. The establishment of nuclear organization in mouse embryos is orchestrated by multiple epigenetic pathways.
  4. Three-dimensional genome structures of single mammalian sperm.
  5. The building blocks of embryo models: embryonic and extraembryonic stem cells.
  6. Basal Xenobot transcriptomics reveals changes and novel control modality in cells freed from organismal influence.
  1. Dev Cell. 2025 Apr 16. pii: S1534-5807(25)00179-0. [Epub ahead of print]
    RIF1 controls replication timing in early mouse embryos independently of lamina-associated nuclear organization.
    Tsunetoshi Nakatani, Tamas Schauer, Mrinmoy Pal, Andreas Ettinger, Luis Altamirano-Pacheco, Julia Zorn, David M Gilbert, Maria-Elena Torres-Padilla.
      Cells must duplicate their genome before they divide to ensure equal transmission of genetic information. The genome is replicated with a defined temporal order, replication timing (RT), which is cell-type specific and linked to 3D-genome organization. During mammalian development, RT is initially not well defined and becomes progressively consolidated from the 4-cell stage. However, the molecular regulators are unknown. Here, by combining loss-of-function analysis with genome-wide investigation of RT in mouse embryos, we identify Rap1 interacting factor 1 (RIF1) as a regulator of the progressive consolidation of RT. Embryos without RIF1 show DNA replication features of an early, more totipotent state. RIF1 regulates the progressive stratification of RT values and its depletion leads to global RT changes and a more heterogeneous RT program. Developmental RT changes are disentangled from changes in transcription and nuclear organization, specifically nuclear lamina association. Our work provides molecular understanding of replication and genome organization at the beginning of mammalian development.
    Keywords:  RIF1; early mouse embryos; lamina-associated domains; replication fork speed; replication timing; single-cell Repli-seq
    DOI:  https://doi.org/10.1016/j.devcel.2025.03.016
  2. Cell Prolif. 2025 Apr 18. e70039
    Deciphering Sequence Determinants of Zygotic Genome Activation Genes: Insights From Machine Learning and the ZGAExplorer Platform.
    Jixiang Xing, Siqi Yang, Yuchao Liang, Pengwei Hu, Bingjie Dai, Hanshuang Li, Yongqiang Xing, Yongchun Zuo.
      The mammalian life cycle initiates with the transition of genetic control from the maternal to the embryonic genome during zygotic genome activation (ZGA), which becomes pivotal for development. Nevertheless, understanding the conservation of genes and transcription factors (TFs) that underlie mammalian ZGA remains limited. Here, we compiled a comprehensive set of ZGA genes from mice, humans, pigs, bovines and goats, including Nr5a2 and TPRX1/2. The identification of 111 homologous genes through comparative analyses was followed by the discovery of a conserved genetic coding region, suggesting potential sequence preferences for ZGA genes. Notably, an interpretable machine learning model based on k-mer core features showed excellent performance in predicting ZGA genes (area under the ROC curve [AUC] > 0.81), revealing abundant and intricate 6-base sequence specific patterns and potential binding TFs, including motifs from NR5A2 and TPRX1/2. Further analysis demonstrated that gene sequence features and epigenetic modification features play equally important roles in regulating ZGA genes. Ultimately, we developed the ZGAExplorer platform to provide an invaluable resource for screening ZGA genes. Our study unravels the sequence determinants of ZGA genes across species through multi-omics data integration and machine learning, yielding insights into ZGA regulatory mechanisms and embryonic developmental arrest.
    Keywords:  epigenetic modification; gene conservation; machine learning; sequence specificity; zygotic genome activation
    DOI:  https://doi.org/10.1111/cpr.70039
  3. Cell. 2025 Apr 15. pii: S0092-8674(25)00396-4. [Epub ahead of print]
    The establishment of nuclear organization in mouse embryos is orchestrated by multiple epigenetic pathways.
    Mrinmoy Pal, Tamas Schauer, Adam Burton, Tsunetoshi Nakatani, Federico Pecori, Alicia Hernández-Giménez, Iliya Nadelson, Marc A Marti-Renom, Maria-Elena Torres-Padilla.
      The folding of the genome in the 3D nuclear space is fundamental for regulating all DNA-related processes. The association of the genome with the nuclear lamina into lamina-associated domains (LADs) represents the earliest feature of nuclear organization during development. Here, we performed a gain-of-function screen in mouse embryos to obtain mechanistic insights. We find that perturbations impacting histone H3 modifications, heterochromatin, and histone content are crucial for the establishment of nuclear architecture in zygotes and/or 2-cell-stage embryos. Notably, some perturbations exerted differential effects on zygotes versus 2-cell-stage embryos. Moreover, embryos with disrupted LADs can rebuild nuclear architecture at the 2-cell stage, indicating that the initial establishment of LADs in zygotes might be dispensable for early development. Our findings provide valuable insights into the functional interplay between chromatin and structural components of the nucleus that guide genome-lamina interactions during the earliest developmental stages.
    Keywords:  3D genome organization; LAD; MZT; ZGA; epigenetics; mouse embryo; nuclear architecture
    DOI:  https://doi.org/10.1016/j.cell.2025.03.044
  4. Nat Commun. 2025 Apr 23. 16(1): 3805
    Three-dimensional genome structures of single mammalian sperm.
    Heming Xu, Yi Chi, Changjian Yin, Cheng Li, Yujie Chen, Zhiyuan Liu, Xiaowen Liu, Hao Xie, Zi-Jiang Chen, Han Zhao, Keliang Wu, Shigang Zhao, Dong Xing.
      The three-dimensional (3D) organization of chromosomes is crucial for packaging a large mammalian genome into a confined nucleus and ensuring proper nuclear functions in somatic cells. However, the packaging of the much more condensed sperm genome is challenging to study with traditional imaging or sequencing approaches. In this study, we develop an enhanced chromosome conformation capture assay, and resolve the 3D whole-genome structures of single mammalian sperm. The reconstructed genome structures accurately delineate the species-specific nuclear morphologies for both human and mouse sperm. We discover that sperm genomes are divided into chromosomal territories and A/B compartments, similarly to somatic cells. However, neither human nor mouse sperm chromosomes contain topologically associating domains or chromatin loops. These results suggest that the fine-scale chromosomal organization of mammalian sperm fundamentally differs from that of somatic cells. The discoveries and methods established in this work will be valuable for future studies of sperm related infertility.
    DOI:  https://doi.org/10.1038/s41467-025-59055-z
  5. Cell Discov. 2025 Apr 22. 11(1): 40
    The building blocks of embryo models: embryonic and extraembryonic stem cells.
    Hongan Ren, Xiaojie Jia, Leqian Yu.
      The process of a single-celled zygote developing into a complex multicellular organism is precisely regulated at spatial and temporal levels in vivo. However, understanding the mechanisms underlying development, particularly in humans, has been constrained by technical and ethical limitations associated with studying natural embryos. Harnessing the intrinsic ability of embryonic stem cells (ESCs) to self-organize when induced and assembled, researchers have established several embryo models as alternative approaches to studying early development in vitro. Recent studies have revealed the critical role of extraembryonic cells in early development; and many groups have created more sophisticated and precise ESC-derived embryo models by incorporating extraembryonic stem cell lines, such as trophoblast stem cells (TSCs), extraembryonic mesoderm cells (EXMCs), extraembryonic endoderm cells (XENs, in rodents), and hypoblast stem cells (in primates). Here, we summarize the characteristics of existing mouse and human embryonic and extraembryonic stem cells and review recent advancements in developing mouse and human embryo models.
    DOI:  https://doi.org/10.1038/s41421-025-00780-6
  6. Commun Biol. 2025 Apr 22. 8(1): 646
    Basal Xenobot transcriptomics reveals changes and novel control modality in cells freed from organismal influence.
    Vaibhav P Pai, Léo Pio-Lopez, Megan M Sperry, Patrick Erickson, Parande Tayyebi, Michael Levin.
      Would transcriptomes change if cell collectives acquired a novel morphogenetic and behavioral phenotype in the absence of genomic editing, transgenes, heterologous materials, or drugs? We investigate the effects of morphology and nascent emergent life history on gene expression in the basal (no engineering, no sculpting) form of Xenobots -autonomously motile constructs derived from Xenopus embryo ectodermal cell explants. To investigate gene expression differences between cells in the context of an embryo with those that have been freed from instructive signals and acquired novel lived experiences, we compare transcriptomes of these basal Xenobots with age-matched Xenopus embryos. Basal Xenobots show significantly larger inter-individual gene variability than age-matched embryos, suggesting increased exploration of the transcriptional space. We identify at least 537 (non-epidermal) transcripts uniquely upregulated in these Xenobots. Phylostratigraphy shows a majority of transcriptomic shifts in the basal Xenobots towards evolutionarily ancient transcripts. Pathway analyses indicate transcriptomic shifts in the categories of motility machinery, multicellularity, stress and immune response, metabolism, thanatotranscriptome, and sensory perception of sound and mechanical stimuli. We experimentally confirm that basal Xenobots respond to acoustic stimuli via changes in behavior. Together, these data may have implications for evolution, biomedicine, and synthetic morphoengineering.
    DOI:  https://doi.org/10.1038/s42003-025-08086-9
This page is being maintained by Thomas Krichel. It was last updated on 2025‒06‒15 at 8:52.