bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–02–22
nine papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Global reorganization of genome architecture at the transition to gametogenesis.
  2. Z-DNA formation regulates the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization.
  3. Extrusion fountains are hallmarks of chromosome organization emerging upon zygotic genome activation.
  4. SETDB1 enables development beyond cleavage stages by extinguishing the MERVL-driven two-cell totipotency transcriptional program in the mouse embryo.
  5. Non-invasive ovulation tracking enables genetic engineering in wild rodents.
  6. Tdrd6a and Tdrd6b together are required for germ plasm formation.
  7. High-sensitivity in situ detection of Sox21 reveals transcript asymmetry from the zygote stage.
  8. Harnessing the Power of Drosophila Primordial Germ Cell Migration.
  9. The discovery of the mammalian fusome.
  1. Nat Struct Mol Biol. 2026 Feb 20.
    Global reorganization of genome architecture at the transition to gametogenesis.
    Tien-Chi Huang, Maria Rigau, Valeriya Malysheva, Chad Whilding, Stella Siciliani, Jingyu Li, Irina Balaguer Balsells, Pavel Artemov, Camille Dion, Mikhail Spivakov, Juan M Vaquerizas, Petra Hajkova.
      Global epigenetic resetting in the gonadal primordial germ cells (PGCs) enables transition from early PGCs to gametogenesis and eventual restoring of totipotency after fertilization. This reprogramming process involves global DNA demethylation, changes in nuclear morphology and remodeling of repressive histone modifications. Here, using combined cytological and Hi-C-based methods, we reveal that, following the epigenetic reprogramming and concomitant with their commitment to gametogenesis, premeiotic gonadal germ cells display a distinct chromosome and genome architecture. This involves separation of individual chromosomes, anchoring of centromeres at the nuclear periphery, reduction in interchromosome interactions and disentangling of chromosome ends. Furthermore, genome-wide contact mapping documents remodeling of the three-dimensional (3D) genome architecture across all observable levels, including disruption of topologically associating domains (TADs), loss of detectable loops and reduced active-active compartment interactions. We further show that the diminished TADs correlate with the reduced levels of CCCTC-binding factor, thus providing an in vivo physiological model to understand genome folding principles. Lastly, we show that PGC-like cells, derived from embryonic stem cells, do not exhibit the same chromatin organization as embryonic germ cells. Collectively, our findings uncover the existence of a distinct chromatin architecture in premeiotic male and female gonadal germ cells and show that, alongside global DNA demethylation, the germline epigenetic reprogramming involves erasure of memory at the genome architectural level through profound reorganization of the 3D genome.
    DOI:  https://doi.org/10.1038/s41594-026-01747-1
  2. Nat Struct Mol Biol. 2026 Feb 17.
    Z-DNA formation regulates the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization.
    Shireen Shajahan, Yann Loe-Mie, Laure Asselin, Marion Salmon-Legagneur, Tatiana Traboulsi, Agnès Thierry, Anne Dejean, Jack-Christophe Cossec.
      The progression from the one-cell to the two-cell stage constitutes a remarkable transition, accompanied by the activation of a specific set of embryonic genes, epigenome reprogramming and nuclear architecture reorganization. Some of these characteristics are recapitulated in vitro with the spontaneous emergence of two-cell-like cells from mouse embryonic stem cells, which exhibit a transcriptomic signature resembling the two-cell stage, including the expression of genes such as Dux, Zscan4 and the repetitive element MERVL, as well as a more relaxed chromatin state. Here we show that interchromosomal and intrachromosomal interactions driven by Zscan4 chromatin factors form during this transition and segregate into a distinct genomic compartment, the Z compartment, independently of cohesin and CCCTC-binding factor. Mechanistically, the formation of Z-DNA, an alternative DNA conformation regulated by polyamine levels, appears to promote the emergence of totipotent-like cells and the establishment of the Z compartment. This compartment is characterized by a decrease in active histone marks and a reduced expression of genes associated with differentiation and late developmental processes. Overall, these findings suggest that Z-DNA formation may have a dual role, first in initiating zygotic genome activation (ZGA) and later in guiding genome compartmentalization to safeguard the totipotent-like state by restricting the expression of non-ZGA genes within a permissive chromatin environment.
    DOI:  https://doi.org/10.1038/s41594-026-01751-5
  3. Nat Commun. 2026 Feb 14.
    Extrusion fountains are hallmarks of chromosome organization emerging upon zygotic genome activation.
    Aleksandra Galitsyna, Sergey V Ulianov, Mariia Bazarevich, Nikolai S Bykov, Marina Veil, Meijiang Gao, Kristina Perevoschikova, Mikhail S Gelfand, Sergey V Razin, Leonid Mirny, Daria Onichtchouk.
      The initiation of gene expression during development, known as zygotic genome activation (ZGA), is accompanied by massive changes in chromosome organization. However, the earliest events of chromosome folding and their functional roles remain unclear. Using Hi-C on zebrafish embryos, we discovered that chromosome folding begins early in development with the formation of fountains, distinct elements of chromosome organization. Emerging preferentially at enhancers, fountains show an initial accumulation of cohesin, which later redistributes to CTCF sites at TAD borders. Knockouts of pioneer transcription factors driving ZGA enhancers cause a specific loss of fountains, establishing a causal link between enhancer activation and fountain formation. Polymer simulations demonstrate that fountains may arise as sites of facilitated cohesin loading, requiring two-sided but desynchronized loop extrusion, potentially caused by cohesin collisions with obstacles or internal switching. Moreover, we detected cohesin-dependent fountain patterns at enhancers in mouse cells and found them reemerging with cohesin loading after mitosis. Altogether, fountains represent enhancer-specific elements of chromosome organization and suggest that chromosome folding during development and after cell division starts with facilitated cohesin loading. Observations in multiple systems further support facilitated loading at enhancers as a widespread phenomenon.
    DOI:  https://doi.org/10.1038/s41467-026-69105-9
  4. Elife. 2026 Feb 16. pii: RP109248. [Epub ahead of print]15
    SETDB1 enables development beyond cleavage stages by extinguishing the MERVL-driven two-cell totipotency transcriptional program in the mouse embryo.
    Tie-Bo Zeng, Zhen Fu, Mary F Majewski, Ji Liao, Marie Adams, Piroska E Szabó.
      Loss of maternal SETDB1, a histone H3K9 methyltransferase, leads to developmental arrest prior to implantation, with very few mouse embryos advancing beyond the eight-cell stage, which is currently unexplained. We genetically investigate SETDB1's role in the epigenetic control of the transition from totipotency to pluripotency-a process demanding precise timing and forward directionality. Through single-embryo total RNA sequencing of two-cell and eight-cell embryos, we find that Setdb1mat-/+ embryos fail to extinguish one-cell and two-cell transient genes-alongside persistent expression of MERVL retroelements and MERVL-driven chimeric transcripts that define the totipotent state in mouse two-cell embryos. Comparative bioinformatics reveals that SETDB1 acts at MT2 LTRs and MERVL-driven chimeric transcripts, which normally acquire H3K9me3 during early development. The dysregulated targets substantially overlap with DUXBL-responsive genes, indicating a shared regulatory pathway for silencing the two-cell transcriptional program. We establish maternal SETDB1 as a critical chromatin regulator required to extinguish retroelement-driven totipotency networks and ensure successful preimplantation development.
    Keywords:  MERVL; SETDB1; genetics; genomics; maternal effect; mouse; preimplantation; single embryo total RNAseq; totipotency
    DOI:  https://doi.org/10.7554/eLife.109248
  5. Cell Rep Methods. 2026 Feb 17. pii: S2667-2375(26)00011-1. [Epub ahead of print] 101311
    Non-invasive ovulation tracking enables genetic engineering in wild rodents.
    Joanna Buchthal, Emma J Chory, Zachary Hill, Christy Dennison, Boqiang Tu, Rick P Wierenga, Çağrı Çevrim, Stefan Golas, Gabriel Meier, Tammy C T Lan, Hattie Chung, Magalie Boucher, Sam R Telford, Kara L McKinley, Styliani Markoulaki, Rudolf Jaenisch, Kevin M Esvelt.
      Many non-model rodent species are inaccessible to genetic engineering due to our limited understanding of their reproductive biology. Here, we present a low-cost, camera-based estrous-tracking technology that enables transgenesis in the white-footed mouse Peromyscus leucopus, a key reservoir for Lyme disease. We demonstrate the efficient generation of pregnant and pseudopregnant mice via timed ovulation, provide protocols for embryo generation, cultivation, microinjection, and transplantation as well as an accurate developmental timeline, and report the first engineered Peromyscus. The same technology successfully tracked conserved estrous-linked cycling behavior in other rodents, including hamsters. Finally, estrous tracking differentiated reproductively healthy, geriatric female Peromyscus from those with declining fertility based solely on their activity, providing a non-invasive method for studying reproductive senescence. Collectively, these tools represent a critical resource for engineering non-model rodents, advance the long-lived Peromyscus as a model organism, and will prove essential to heritably immunizing wild rodent populations against Lyme disease.
    Keywords:  CP: developmental biology; CP: genetics; CRISPR-Cas9 transgenesis; Lyme disease reservoir; Peromyscus leucopus; automated activity monitoring; estrous cycle tracking; machine learning in cytology; non-invasive phenotyping; non-model rodents; reproductive senescence; white-footed mouse
    DOI:  https://doi.org/10.1016/j.crmeth.2026.101311
  6. Development. 2026 Feb 20. pii: dev.204545. [Epub ahead of print]
    Tdrd6a and Tdrd6b together are required for germ plasm formation.
    Alessandro Consorte, Joanna Michowicz, Fiona Carey, Martin M Möckel, Yasmin El Sherif, Nadine Wittkopp, René F Ketting.
      Germ cell specification is often driven by germplasm (Gp): phase-separation-based structures in the embryo, formed by maternal RNA and proteins. In the zebrafish, these oocyte-derived factors form a large structure known as the Balbiani body (Bb), which is also required for proper oocyte polarization. How the formation of these entities is regulated, especially in vertebrates, remains unclear. In this study, we show that two multi-Tudor proteins, Tdrd6a and Tdrd6b, are together required for Gp formation in zebrafish. While the Bb in the oocyte is affected in absence of both Tdrd6a, and not Tdrd6b, this does not affect oocyte functionality. In contrast, Gp is largely dispersed at the 4-cell stage, resulting in the absence of primordial germ cells during later development and sterility. Furthermore, we show that the Prion-like domain of Tdrd6b is relevant for Tdrd6b aggregation as well as for its interaction with Buc and that this modulated by Tdrd6b Tudor domains. The implication of Tdrd6a and Tdrd6b in Gp stability is an important step in our understanding of how this phase-separated structure is controlled during development.
    Keywords:  Bucky ball; Germ cell; Germplasm; Tudor domain; Zebrafish
    DOI:  https://doi.org/10.1242/dev.204545
  7. Dev Biol. 2026 Feb 13. pii: S0012-1606(26)00030-8. [Epub ahead of print]533 112-120
    High-sensitivity in situ detection of Sox21 reveals transcript asymmetry from the zygote stage.
    Estefania Sanchez-Vasquez, Gyda Nawarungruang, Maciej Meglicki, Marianne E Bronner, Magdalena Zernicka-Goetz.
      The first lineage decision in mammalian development segregates embryonic and extra-embryonic fates, yet the timing of this specification remains under debate. While our previous lineage tracing studies in mice and human suggested that this decision is initiated as early as the 2-cell stage, prevailing models place its onset to the 16-cell stage embryo when the first inside cells form. In mice, we have found that heterogeneous expression of Sox21 at the 4-cell stage contributes to fate specification, with higher SOX21 levels biasing cells toward embryonic fates (future foetus). Here, we investigated whether this heterogeneity originates even earlier. Because conventional single-cell RNA-seq has failed to detect mRNA asymmetries prior to the 4-cell stage, we employed a more sensitive approach, confocal imaging combined with hybridization chain reaction (HCR), to track Sox21 mRNA expression from the zygote through the 4-cell stage. This single-molecule technique revealed pronounced heterogeneity in Sox21 transcript levels as early as the 2-cell stage. Intriguingly, Sox21 mRNA appears to be preferentially expressed from the male pronucleus during minor zygotic genome activation, perhaps as a consequence of H3K27me3 enrichment in the maternal pronuclei and given that haploid parthenogenetic embryos lack SOX21 protein at the 4-cell stage. These findings provide evidence that Sox21 mRNA heterogeneity arises earlier than previously recognized, namely at the 2-cell stage. Our work supports the emerging view that spatial mRNA distribution, long appreciated in non-mammalian embryos, might also contribute to lineage specification in mammals.
    DOI:  https://doi.org/10.1016/j.ydbio.2026.02.002
  8. Cold Spring Harb Perspect Biol. 2026 Feb 17. pii: a041800. [Epub ahead of print]
    Harnessing the Power of Drosophila Primordial Germ Cell Migration.
    Lacy J Barton, Benjamin Lin.
      Primordial germ cells (PGCs) are embryonic germline precursors of sperm and egg that connect one generation to the next. In many animals, maintaining this intergenerational connection requires long-distance PGC migration across varied tissues during embryonic development. How PGCs traverse these dynamic cellular terrains and respond to a select number of cues while ignoring others remains a mystery. This review describes the molecular mechanisms underlying PGC migration in Drosophila melanogaster, focusing on cell motility modes and the myriad of signals and cells PGCs interact with during their journey. We describe the tools and techniques available in Drosophila to assess and manipulate migrating PGCs and the surrounding cells they encounter. As PGC migration entails wide-ranging cell behaviors from transepithelial migration to directed cell motility across divergent tissues, harnessing the power of Drosophila can provide fundamental insights into how cell movement in vivo drives health and disease.
    DOI:  https://doi.org/10.1101/cshperspect.a041800
  9. Elife. 2026 Feb 18. pii: e110713. [Epub ahead of print]15
    The discovery of the mammalian fusome.
    Michael Buszczak, Anirban Dasgupta.
      The presence of an organelle called the fusome in species as diverse as Drosophila and mammals indicates an ancient, conserved programme of germ cell development.
    Keywords:  apical-basal polarity; cell cycle; developmental biology; fusome; germline cyst; mouse; oocyte development
    DOI:  https://doi.org/10.7554/eLife.110713
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