bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–01–26
fifteen papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Transcriptional Integration of Meiotic Prophase I Progression and Early Oocyte Differentiation.
  2. Exocyst complex component 1 (Exoc1) loss in dormant oocyte disrupts c-KIT and growth differentiation factor (GDF9) subcellular localization and causes female infertility in mice.
  3. Dynamic molecular architecture of the synaptonemal complex.
  4. Temporal and regional X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing.
  5. The role of KLF4 in human primordial germ cell development.
  6. WDR74-Mediated Ribosome Biogenesis and Proteome Dynamics During Mouse Preimplantation Development.
  7. Mouse totipotent blastomere-like cells model embryogenesis from zygotic genome activation to post implantation.
  8. Landscape and regulation of new protein translation in the early C. elegans embryo.
  9. Complete human recombination maps.
  10. Recent insights into the in vitro culture systems for mammalian embryos.
  11. Rapid human oogonia-like cell specification via transcription factor-directed differentiation.
  12. Key glycometabolism during oocyte maturation and early embryonic development.
  13. The maternal X chromosome affects cognition and brain ageing in female mice.
  14. An atlas of transcription initiation reveals regulatory principles of gene and transposable element expression in early mammalian development.
  15. A biophysical basis for the spreading behavior and limited diffusion of Xist.
  1. bioRxiv. 2025 Jan 06. pii: 2025.01.06.631470. [Epub ahead of print]
    Transcriptional Integration of Meiotic Prophase I Progression and Early Oocyte Differentiation.
    Kimberly M Abt, Myles A Bartholomew, Anna Nixon, Hanna E Richman, Megan A Gura, Kimberly A Seymour, Richard N Freiman.
      Female reproductive senescence results from the regulated depletion of a finite pool of oocytes called the ovarian reserve. This pool of oocytes is initially established during fetal development, but the oocytes that comprise it must remain quiescent for decades until they are activated during maturation in adulthood. In order for developmentally competent oocytes to populate the ovarian reserve they must successfully initiate both meiosis and oogenesis. As the factors that regulate the timing and fidelity of these early events remain elusive, we assessed the precise function and timing of the transcriptional regulator TAF4b during meiotic prophase I progression in mouse fetal oocytes. Compared to matched controls, E14.5 Taf4b-deficient oocytes enter meiosis I in a timely manner however, their subsequent progression through the pachytene-to-diplotene transition of meiotic prophase I is compromised. Moreover, this disruption of meiotic progression is associated with the reduced ability of Taf4b-deficient oocytes to repair double-strand DNA breaks. Transcriptional profiling of Taf4b-deficient oocytes reveals that between E16.5 and E18.5 these oocytes fail to coordinate the reduction of meiotic gene expression and the induction of oocyte differentiation genes. These studies reveal that TAF4b promotes the formation of the ovarian reserve in part by orchestrating the timely transition to meiosis I arrest and oocyte differentiation, which are often perceived as separate events.
    DOI:  https://doi.org/10.1101/2025.01.06.631470
  2. Cell Death Discov. 2025 Jan 20. 11(1): 17
    Exocyst complex component 1 (Exoc1) loss in dormant oocyte disrupts c-KIT and growth differentiation factor (GDF9) subcellular localization and causes female infertility in mice.
    Chi Lieu Kim Nguyen, Yumeno Kuba, Hoai Thu Le, Hossam Hassan Shawki, Natsuki Mikami, Madoka Aoki, Nanako Yasuhara, Hayate Suzuki, Saori Mizuno-Iijima, Shinya Ayabe, Yuki Osawa, Tomoyuki Fujiyama, Tra Thi Huong Dinh, Miyuki Ishida, Yoko Daitoku, Yoko Tanimoto, Kazuya Murata, Woojin Kang, Masatsugu Ema, Yuji Hirao, Atsuo Ogura, Satoru Takahashi, Fumihiro Sugiyama, Seiya Mizuno.
      A limited number of female germ cells support reproduction in many mammals. The follicle, composed of oocytes and supporting granulosa cells, forms the basis of oogenesis. Crosstalk between oocytes and granulosa cells is essential for the formation, dormancy, re-awakening, and maturation of oocytes. The oocyte expresses c-KIT and growth differentiation factor-9 (GDF-9), which are major factors in this crosstalk. The downstream signalling pathways of c-KIT and GDF-9 have been well-documented; however, their intra-oocyte trafficking pathway remains unclear. Our study reveals that the exocyst complex, a heterotetrameric protein complex important for tethering in vesicular transport, is important for proper intra-oocyte trafficking of c-KIT and GDF9 in mice. We found that depletion of oocyte-specific EXOC1, a component of the exocyst complex, impaired oocyte re-awakening and cyst breakdown, and inhibited granulosa cell proliferation during follicle growth. The c-KIT receptor is localised on the oocyte plasma membrane. The oocyte-specific Kit conditional knockout mice were reported to exhibit impaired oocyte re-awakening and reduced oocyte cyst breakdown. GDF9 is a protein secreted extracellularly in the oocyte. Previous studies have shown that Gdf9 knockout mice impaired proliferation and granulosa cell multilayering in growing follicles. We found that both c-KIT and GDF9 abnormally stuck in the EXOC1-depleted oocyte cytoplasm. These abnormal phenotypes were also observed in oocytes depleted of exocyst complex members EXOC3 and EXOC7. These results clearly show that the exocyst complex is essential for proper intra-oocyte trafficking of c-KIT and GDF9. Inhibition of this complex causes complete loss of female fertility in mice. Our findings build a platform for research related to trafficking mechanisms of vital crosstalk factors for oogenesis.
    DOI:  https://doi.org/10.1038/s41420-025-02291-5
  3. Sci Adv. 2025 Jan 24. 11(4): eadq9374
    Dynamic molecular architecture of the synaptonemal complex.
    Simone Köhler, Michal Wojcik, Ke Xu, Abby F Dernburg.
      During meiosis, pairing between homologous chromosomes is stabilized by the assembly of the synaptonemal complex (SC). The SC ensures the formation of crossovers between homologous chromosomes and regulates their distribution. However, how the SC regulates crossover formation remains elusive. We isolated an unusual mutation in Caenorhabditis elegans that disrupts crossover interference but not SC assembly. This mutation alters the unique C terminal domain of an essential SC protein, SYP-4, a likely ortholog of the vertebrate SC protein SIX6OS1. We use three-dimensional stochastic optical reconstruction microscopy (3D-STORM) to interrogate the molecular architecture of the SC from wild-type and mutant C. elegans animals. Using a probabilistic mapping approach to analyze super-resolution image data, we detect changes in the organization of the synaptonemal complex in wild-type animals that coincide with crossover designation. We also found that our syp-4 mutant perturbs SC architecture. Our findings add to growing evidence that the SC is an active material whose molecular organization contributes to chromosome-wide crossover regulation.
    DOI:  https://doi.org/10.1126/sciadv.adq9374
  4. Nat Struct Mol Biol. 2025 Jan 21.
    Temporal and regional X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing.
    Clara Roidor, Laurène Syx, Emmanuelle Beyne, Peggy Raynaud, Dina Zielinski, Aurélie Teissandier, Caroline Lee, Marius Walter, Nicolas Servant, Karim Chebli, Deborah Bourc'his, M Azim Surani, Maud Borensztein.
      Random X-chromosome inactivation is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long noncoding RNA Xist, occurs in the early embryo and is stably maintained throughout life, although inactivation is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling on developing mouse PGCs, we provide a detailed map of X-linked gene reactivation. Despite the absence of Xist expression, PGCs still harbor a fully silent X chromosome at embryonic day 9.5 (E9.5). Subsequently, X-linked genes undergo gradual and distinct regional reactivation. At E12.5, a substantial part of the inactive X chromosome resists reactivation, retaining an epigenetic memory of its silencing. Our findings define the orchestration of reactivation of the inactive X chromosome, a key event in female PGC reprogramming with direct implications for reproduction.
    DOI:  https://doi.org/10.1038/s41594-024-01469-2
  5. Open Biol. 2025 Jan;15(1): 240214
    The role of KLF4 in human primordial germ cell development.
    Sun-Min Lee, Merrick Pierson Smela, M Azim Surani.
      Primordial germ cells (PGCs) are the founder cells that develop into mature gametes. PGCs emerge during weeks 2-3 of human embryo development. Pluripotency genes are reactivated during PGC specification, including Krüppel-like factor KLF4, but its precise role in PGC development is unclear. Here, we investigated the role of KLF4 in PGC development using our in vitro model for human PGC-like cells (hPGCLCs). We demonstrate that the depletion of KLF4 reduces the efficiency of hPGCLC specification, resulting in hPGCLCs with an aberrant transcriptome. Cut-and-run and transcriptomic analyses reveal that KLF4 represses somatic markers involved in neuronal and endodermal differentiation while promoting the expression of genes associated with PGC specification, such as PAX5, and epigenetic regulators, including DNMT3L and REST. KLF4 targets in hPGCLCs showed significant co-enrichment of motifs for SP and STAT factors, which are known to regulate cell cycle and migration genes. KLF4 contributes to human PGC development by activating genes involved in PGC specification and cell cycle regulation, while repressing somatic genes to maintain PGC identity.
    Keywords:  KLF4; pluripotency factors; primordial germ cells; stem cells
    DOI:  https://doi.org/10.1098/rsob.240214
  6. Genes Cells. 2025 Jan;30(1): e70001
    WDR74-Mediated Ribosome Biogenesis and Proteome Dynamics During Mouse Preimplantation Development.
    Ayaka Kakihara, Marino Maemura, Atsushi Hatano, Masaki Matsumoto, Yu-Ichi Tsukada.
      Preimplantation embryonic development is orchestrated by dynamic changes in the proteome and transcriptome, regulated by mechanisms such as maternal-to-zygotic transition. Here, we employed label-free quantitative proteomics to comprehensively analyze proteome dynamics from germinal vesicle oocytes to blastocysts in mouse embryos. We identified 3490 proteins, including 715 consistently detected across all stages, revealing stage-specific changes in proteins associated with translation, protein modification, and mitochondrial metabolism. Comparison with transcriptomic data highlighted a low correlation between mRNA and protein levels, underscoring the significance of non-transcriptional regulatory mechanisms during early development. Additionally, we analyzed WD repeat-containing protein 74 (WDR74)-deficient embryos generated using CRISPR-Cas9 genome editing. WDR74, a pre-60S ribosome maturation factor, was found to be critical for ribosome biogenesis and cell division. Furthermore, WDR74 deficiency led to a significant reduction in ribosomal protein large subunit and impaired progression beyond the morula stage. Key ribosomal proteins such as ribosomal protein L24 (RPL24) and ribosomal protein L26 (RPL26), which influence cell division timing, were notably affected, while small subunit proteins remained largely unchanged. Taken together, our study demonstrates the utility of integrating genome editing with proteomic analysis to elucidate molecular mechanisms underlying early embryogenesis, and provides new insights into protein-level regulation of preimplantation development.
    Keywords:  pre‐implantation development; pre‐implantation embryo; proteomics; ribosome biogenesis
    DOI:  https://doi.org/10.1111/gtc.70001
  7. Cell Stem Cell. 2025 Jan 10. pii: S1934-5909(24)00446-6. [Epub ahead of print]
    Mouse totipotent blastomere-like cells model embryogenesis from zygotic genome activation to post implantation.
    Bing Peng, Qingyi Wang, Feixiang Zhang, Hui Shen, Peng Du.
      Embryo development begins with zygotic genome activation (ZGA), eventually generating blastocysts for implantation. However, in vitro systems modeling the pre-implantation development are still absent and challenging. Here, we used mouse totipotent blastomere-like cells (TBLCs) to develop spontaneous differentiation and blastoid formation systems, respectively. We found Wnt signaling enabled the rapid expansion of TBLCs and the optimization of their culture medium. We successfully developed a TBLC-spontaneous differentiation system in which mouse TBLCs (mTBLCs) firstly converted into two types of ZGA-like cells (ZLCs) distinguished by Zscan4 expression. Surprisingly, Zscan4-, but not Zscan4+, ZLCs further passed through intermediate 4-cell and then 8-cell/morula stages to produce epiblast, primitive endoderm, and trophectoderm lineages. Significantly, single TBLCs underwent expansion, compaction, and polarization to efficiently generate blastocyst-like structures and even post-implantation egg-cylinder-like structures. Conclusively, we established TBLC-based differentiation and embryo-like structure formation systems to model early embryonic development, offering criteria for evaluating and understanding totipotency.
    Keywords:  Wnt signaling; blastoid; preimplantation; splicing inhibition; spontaneous differentiation; totipotent; totipotent blastomere-like cell
    DOI:  https://doi.org/10.1016/j.stem.2024.12.006
  8. bioRxiv. 2025 Jan 07. pii: 2024.12.13.628416. [Epub ahead of print]
    Landscape and regulation of new protein translation in the early C. elegans embryo.
    Yash Shukla, Vighnesh Ghatpande, Cindy F Hu, Daniel J Dickinson, Can Cenik.
      Translation of maternal mRNAs is crucial for early embryonic development. In C. elegans, cell fates become determined from the first division without new transcription, making this organism ideal for studying post-transcriptional regulation of lineage specification. Using low-input ribosome profiling combined with RNA sequencing on precisely staged embryos, we measured protein translation during the first four cell cycles of C. elegans development. We uncovered stage-specific patterns of developmentally coordinated translational regulation. We found that mRNA localization correlates with translational efficiency, though initial translational repression in germline precursors occurs prior to P-granule association. The RNA-binding protein OMA-1 emerged as a key regulator of translational efficiency in a stage-specific manner. These findings illuminate how post-transcriptional mechanisms shape the embryonic proteome to direct cell differentiation, with implications for understanding similar regulation across species where maternal factors guide early development.
    DOI:  https://doi.org/10.1101/2024.12.13.628416
  9. Nature. 2025 Jan 22.
    Complete human recombination maps.
    Gunnar Palsson, Marteinn T Hardarson, Hakon Jonsson, Valgerdur Steinthorsdottir, Olafur A Stefansson, Hannes P Eggertsson, Sigurjon A Gudjonsson, Pall I Olason, Arnaldur Gylfason, Gisli Masson, Unnur Thorsteinsdottir, Patrick Sulem, Agnar Helgason, Daniel F Gudbjartsson, Bjarni V Halldorsson, Kari Stefansson.
      Human recombination maps are a valuable resource for association and linkage studies and crucial for many inferences of population history and natural selection. Existing maps1-5 are based solely on cross-over (CO) recombination, omitting non-cross-overs (NCOs)-the more common form of recombination6-owing to the difficulty in detecting them. Using whole-genome sequence data in families, we estimate the number of NCOs transmitted from parent to offspring and derive complete, sex-specific recombination maps including both NCOs and COs. Mothers have fewer but longer NCOs than fathers, and oocytes accumulate NCOs in a non-regulated fashion with maternal age. Recombination, primarily NCO, is responsible for 1.8% (95% confidence interval: 1.3-2.3) and 11.3% (95% confidence interval: 9.0-13.6) of paternal and maternal de novo mutations, respectively, and may drive the increase in de novo mutations with maternal age. NCOs are substantially more prominent than COs in centromeres, possibly to avoid large-scale genomic changes that may cause aneuploidy. Our results demonstrate that NCOs highlight to a much greater extent than COs the differences in the meiotic process between the sexes, in which maternal NCOs may reflect the safeguarding of oocytes from infancy until ovulation.
    DOI:  https://doi.org/10.1038/s41586-024-08450-5
  10. Curr Opin Genet Dev. 2025 Jan 18. pii: S0959-437X(25)00001-2. [Epub ahead of print]91 102309
    Recent insights into the in vitro culture systems for mammalian embryos.
    Zhiyuan Guo, Wentao Zhao, Hongmei Wang, Jinglei Zhai.
      Mammalian early embryonic development is the cornerstone for a healthy life. Any aberrations during early embryonic development may lead to adverse pregnancy outcomes. Therefore, the comprehensive study of embryonic developmental events is essential for understanding biological and pathological pregnancy. However, due to mammalian embryo development taking place in the uterus, it is hard to directly observe the developing embryos that are undergoing dramatic and complex morphologies, proliferation, and differentiation. The in vitro culture (IVC) of mammalian embryos is a pivotal model for studying developmental events. Recent advancements in establishing long-term culture systems for early mammalian embryos have allowed researchers to culture human embryos up to the embryonic day (E) 14 ethical limitations and extend mouse and macaque embryos to early organogenesis. Here, we review the development of IVC systems for mammalian embryos, emphasize the important improvements in culture elements, and offer our perspectives on potential future optimizations of IVC systems.
    DOI:  https://doi.org/10.1016/j.gde.2025.102309
  11. EMBO Rep. 2025 Jan 23.
    Rapid human oogonia-like cell specification via transcription factor-directed differentiation.
    Merrick Pierson Smela, Christian C Kramme, Patrick R J Fortuna, Bennett Wolf, Shrey Goel, Jessica Adams, Carl Ma, Sergiy Velychko, Ursula Widocki, Venkata Srikar Kavirayuni, Tianlai Chen, Sophia Vincoff, Edward Dong, Richie E Kohman, Mutsumi Kobayashi, Toshi Shioda, George M Church, Pranam Chatterjee.
      The generation of germline cells from human induced pluripotent stem cells (hiPSCs) represents a milestone toward in vitro gametogenesis. Methods to recapitulate germline development beyond primordial germ cells in vitro have relied on long-term cell culture, such as 3-dimensional organoid co-culture for ~four months. Using a pipeline with highly parallelized screening, this study identifies combinations of TFs that directly and rapidly convert hiPSCs to induced oogonia-like cells (iOLCs). We demonstrate that co-expression of five TFs - namely, ZNF281, LHX8, SOHLH1, ZGLP1, and ANHX, induces high efficiency DDX4-positive iOLCs in only four days in a feeder-free monolayer culture condition. We also show improved production of human primordial germ cell-like cells (hPGCLCs) from hiPSCs by expression of DLX5, HHEX, and FIGLA. We characterize these TF-based iOLCs and hPGCLCs via gene and protein expression analyses and demonstrate their similarity to in vivo and in vitro-derived oogonia and primordial germ cells. Together, these results identify new regulatory factors that enhance human germ cell specification in vitro, and further establish unique computational and experimental tools for human in vitro oogenesis research.
    Keywords:  Differentiation; Induced Pluripotent Stem Cells; Oogonia; Primordial Germ Cells; Transcription Factors
    DOI:  https://doi.org/10.1038/s44319-025-00371-2
  12. Reproduction. 2025 Jan 01. pii: REP-24-0275. [Epub ahead of print]
    Key glycometabolism during oocyte maturation and early embryonic development.
    Yichuan Zhang, Tianjie Li, Yibo Wang, Yang Yu.
      In recent decades, it has become increasingly clear that mammalian gametes and early embryos are highly sensitive to metabolic substrates. With advances in single-cell sequencing, metabolomics, and bioinformatics, we now recognize that metabolic pathways not only meet cellular energy demands but also play a critical role in cell proliferation, differentiation, and fate determination. Investigating metabolic processes during oocyte maturation and early embryonic development is thus essential to advancing reproductive medicine and embryology. This review highlights the intricate metabolic pathways, particularly glucose metabolism, that drive the transition from oocyte to embryo. These processes involve a complex interaction of signaling pathways, nutrient availability, and environmental factors, with glucose metabolism not only providing essential energy but also offering a variety of metabolic substrates and intermediates that regulate developmental events, influence cell signaling, and impact epigenetic modifications. This article emphasizes that future research will focus on regulating maternal metabolic environments and non-invasive metabolic monitoring of embryonic systems, particularly glucose metabolism, with promising opportunities to improve embryo selection and personalized assisted reproductive technologies, ultimately enhancing fertility treatment outcomes.
    DOI:  https://doi.org/10.1530/REP-24-0275
  13. Nature. 2025 Jan 22.
    The maternal X chromosome affects cognition and brain ageing in female mice.
    Samira Abdulai-Saiku, Shweta Gupta, Dan Wang, Francesca Marino, Arturo J Moreno, Yu Huang, Deepak Srivastava, Barbara Panning, Dena B Dubal.
      Female mammalian cells have two X chromosomes, one of maternal origin and one of paternal origin. During development, one X chromosome randomly becomes inactivated1-4. This renders either the maternal X (Xm) chromosome or the paternal X (Xp) chromosome inactive, causing X mosaicism that varies between female individuals, with some showing considerable or complete skew of the X chromosome that remains active5-7. Parent-of-X origin can modify epigenetics through DNA methylation8,9 and possibly gene expression; thus, mosaicism could buffer dysregulated processes in ageing and disease. However, whether X skew or its mosaicism alters functions in female individuals is largely unknown. Here we tested whether skew towards an active Xm chromosome influences the brain and body-and then delineated unique features of Xm neurons and Xp neurons. An active Xm chromosome impaired cognition in female mice throughout the lifespan and led to worsened cognition with age. Cognitive deficits were accompanied by Xm-mediated acceleration of biological or epigenetic ageing of the hippocampus, a key centre for learning and memory, in female mice. Several genes were imprinted on the Xm chromosome of hippocampal neurons, suggesting silenced cognitive loci. CRISPR-mediated activation of Xm-imprinted genes improved cognition in ageing female mice. Thus, the Xm chromosome impaired cognition, accelerated brain ageing and silenced genes that contribute to cognition in ageing. Understanding how Xm impairs brain function could lead to an improved understanding of heterogeneity in cognitive health in female individuals and to X-chromosome-derived pathways that protect against cognitive deficits and brain ageing.
    DOI:  https://doi.org/10.1038/s41586-024-08457-y
  14. Cell. 2025 Jan 16. pii: S0092-8674(24)01426-0. [Epub ahead of print]
    An atlas of transcription initiation reveals regulatory principles of gene and transposable element expression in early mammalian development.
    Marlies E Oomen, Diego Rodriguez-Terrones, Mayuko Kurome, Valeri Zakhartchenko, Lorenza Mottes, Kilian Simmet, Camille Noll, Tsunetoshi Nakatani, Carlos Michel Mourra-Diaz, Irene Aksoy, Pierre Savatier, Jonathan Göke, Eckhard Wolf, Henrik Kaessmann, Maria-Elena Torres-Padilla.
      Transcriptional activation of the embryonic genome (EGA) is a major developmental landmark enabling the embryo to become independent from maternal control. The magnitude and control of transcriptional reprogramming during this event across mammals remains poorly understood. Here, we developed Smart-seq+5' for high sensitivity, full-length transcript coverage and simultaneous capture of 5' transcript information from single cells and single embryos. Using Smart-seq+5', we profiled 34 developmental stages in 5 mammalian species and provide an extensive characterization of the transcriptional repertoire of early development before, during, and after EGA. We demonstrate widespread transposable element (TE)-driven transcription across species, including, remarkably, of DNA transposons. We identify 19,657 TE-driven genic transcripts, suggesting extensive TE co-option in early development over evolutionary timescales. TEs display similar expression dynamics across species and species-specific patterns, suggesting shared and divergent regulation. Our work provides a powerful resource for understanding transcriptional regulation of mammalian development.
    Keywords:  TSS; ZGA; evolutionary conservation; evolutionary genomics; mammalian preimplantation development; transcriptomics; transposable elements
    DOI:  https://doi.org/10.1016/j.cell.2024.12.013
  15. Cell. 2025 Jan 15. pii: S0092-8674(24)01417-X. [Epub ahead of print]
    A biophysical basis for the spreading behavior and limited diffusion of Xist.
    Mingrui Ding, Danni Wang, Hui Chen, Barry Kesner, Niklas-Benedikt Grimm, Uri Weissbein, Anna Lappala, Jiying Jiang, Carlos Rivera, Jizhong Lou, Pilong Li, Jeannie T Lee.
      Xist RNA initiates X inactivation as it spreads in cis across the chromosome. Here, we reveal a biophysical basis for its cis-limited diffusion. Xist RNA and HNRNPK together drive a liquid-liquid phase separation (LLPS) that encapsulates the chromosome. HNRNPK droplets pull on Xist and internalize the RNA. Once internalized, Xist induces a further phase transition and "softens" the HNRNPK droplet. Xist alters the condensate's deformability, adhesiveness, and wetting properties in vitro. Other Xist-interacting proteins are internalized and entrapped within the droplet, resulting in a concentration of Xist and protein partners within the condensate. We attribute LLPS to HNRNPK's RGG and Xist's repeat B (RepB) motifs. Mutating these motifs causes Xist diffusion, disrupts polycomb recruitment, and precludes the required mixing of chromosomal compartments for Xist's migration. Thus, we hypothesize that phase transitions in HNRNPK condensates allow Xist to locally concentrate silencing factors and to spread through internal channels of the HNRNPK-encapsulated chromosome.
    Keywords:  HNRNPK; RGG domain; RepB; Xist RNA; cis-limited spreading; condensates; deformability; droplets; liquid-liquid phase separation; repeat B
    DOI:  https://doi.org/10.1016/j.cell.2024.12.004
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