bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–06–01
twenty papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Condensate-forming eIF4ET ensures adequate levels of meiotic proteins to support oocyte storage.
  2. Disrupted MOS signaling alters meiotic cell cycle regulation and the egg transcriptome.
  3. Micropipette aspiration reveals differential RNA-dependent viscoelasticity of nucleolar subcompartments.
  4. A sperm-oocyte protein partnership required for egg activation in Caenorhabditis elegans.
  5. Chromatin Analyses in Mouse Oocytes and Preimplantation Embryos.
  6. CUT&Tag for Transcription Factor Binding Profiles During Mammalian Zygotic Genome Activation.
  7. Monitoring miRNA Expression and Activity in Mammalian Oocytes and Early Embryos.
  8. RNA multi-omics in single cells reveal rhythmical RNA reshaping during human and mouse oocyte maturation.
  9. Role of ZBED3 in PALD1/PIP2- dependent calcium homeostasis during oocyte maturation.
  10. Non-Redundant Essential Roles of Proteasomal Ubiquitin Receptors Rpn10 and Rpn13 in Germ Cell Formation and Fertility.
  11. Transcriptomic Profile of Early Antral Follicles: Predictive Somatic Gene Markers of Oocyte Maturation Outcome.
  12. Quantifying Nascent Transcription in Early Embryogenesis.
  13. Functional Characterization and Heterogeneity Analysis of Ribosomal Proteins in Mouse Preimplantation Embryos.
  14. Notch controls APC/CFZR-1 to enable accumulation of chromatin regulators in germline stem cells from Caenorhabditis elegans.
  15. Ecdysone regulates phagocytic cell fate of epithelial cells in developing Drosophila eggs.
  16. Transcription-templated assembly of the nucleolus in the Caenorhabditis elegans embryo.
  17. Short-term moderate caloric restriction in the rhesus macaque attenuates markers of ovarian aging in select populations.
  18. Catalytic-dependent and independent functions of the histone acetyltransferase CBP promote pioneer-factor-mediated zygotic genome activation.
  19. hnRNPL phase separation activates PIK3CB transcription and promotes glycolysis in ovarian cancer.
  20. The role of KAT6A in regulating primordial follicle activation in mouse ovary.
  1. Life Sci Alliance. 2025 Aug;pii: e202503387. [Epub ahead of print]8(8):
    Condensate-forming eIF4ET ensures adequate levels of meiotic proteins to support oocyte storage.
    Priyankaa Bhatia, Judith Tafur, Ruchi Amin, Nicole E Familiari, Kan Yaguchi, Vanna M Tran, Alec Bond, Orhan Bukulmez, Jeffrey B Woodruff.
      Animals store oocytes in a dormant state for weeks to decades before ovulation. The homeostatic programs that oocytes use to endure long-term storage are poorly understood. Using female nematodes as a short-lived model, we found that oocyte formation and storage required IFET-1, the conserved eIF4E-transporter protein (eIF4ET). IFET-1 co-assembled with CAR-1 (Lsm14) to form micron-scale condensates in stored oocytes, which dissipated after oocyte activation. Depletion of IFET-1 destabilized the stored oocyte proteome, leading to lower translation, a decline in microtubule maintenance proteins, and errors in microtubule organization and meiotic spindle assembly. Deleting domains within IFET-1 impaired oocyte storage without affecting oocyte formation. Thus, in addition to establishing a healthy oocyte reserve in young mothers, IFET-1 ensures that correct levels of cytoskeletal proteins are maintained as oocytes age. eIF4ET also localized to micron-scale puncta in dormant human oocytes. Our results clarify how eIF4ET maintains the oocyte reserve and further support eIF4ET dysfunction as an upstream cause of embryonic aneuploidy and age-related infertility.
    DOI:  https://doi.org/10.26508/lsa.202503387
  2. Reproduction. 2025 May 01. pii: REP-25-0156. [Epub ahead of print]
    Disrupted MOS signaling alters meiotic cell cycle regulation and the egg transcriptome.
    Gisela Cairo, Olha Kholod, Olivia Palmer, Sophia Meytin, Brittany A Goods, Soni Lacefield.
      Mammalian female meiosis is tightly regulated to produce a developmentally competent egg. Oocytes enter meiosis in the fetal ovary and then arrest at prophase I until sexual maturation. Upon hormonal stimulation, a subset of oocytes resumes meiosis. Oocytes then complete meiosis I, enter metaphase II, and arrest until fertilization, a process essential for egg competency. The MOS kinase is a key regulator of the metaphase II arrest, activating the MAPK signaling cascade. Loss of MOS in female mice disrupts the maintenance of the metaphase II arrest, with some eggs extruding two polar bodies and some dividing beyond anaphase II. To investigate the consequences of the Mos deletion, we performed live imaging and found that mos-/- eggs exhibit transient chromosome separation events in meiosis I, suggesting a role for MOS in coordinating the timing of meiotic divisions. Further analysis showed that new transcription is required for mos-/- eggs to undergo additional divisions but not for second polar body extrusion. Surprisingly, single-egg sequencing revealed extensive differences in gene expression between wildtype and mos-/- eggs, including those with only one polar body. Many differentially expressed genes were involved in cell cycle regulation, including Aurka, Bub3, and Cdk7. Upregulated pathways included metabolism of RNA, transcription, and neddylation. Furthermore, the gene expression profile of mos-/- eggs was markedly different from that of chemically activated wildtype eggs. Our findings demonstrate that MOS plays a crucial role in meiotic cell cycle regulation and helps ensure that the egg maintains the proper transcriptome necessary for developmental competence.
    DOI:  https://doi.org/10.1530/REP-25-0156
  3. Proc Natl Acad Sci U S A. 2025 Jun 03. 122(22): e2407423122
    Micropipette aspiration reveals differential RNA-dependent viscoelasticity of nucleolar subcompartments.
    Holly H Cheng, James V Roggeveen, Huan Wang, Howard A Stone, Zheng Shi, Clifford P Brangwynne.
      The nucleolus is a multiphasic biomolecular condensate that facilitates ribosome biogenesis, a complex process involving hundreds of proteins and RNAs. The proper execution of ribosome biogenesis likely depends on the material properties of the nucleolus. However, these material properties remain poorly understood due to the challenges of in vivo measurements. Here, we use micropipette aspiration (MPA) to directly characterize the viscoelasticity and interfacial tensions of nucleoli within transcriptionally active Xenopus laevis oocytes. We examine the major nucleolar subphases, the outer granular component (GC) and the inner dense fibrillar component (DFC), which itself contains a third small phase known as the fibrillar center (FC). We show that the behavior of the GC is more liquid-like, while the behavior of the DFC/FC is consistent with that of a partially viscoelastic solid. To determine the role of ribosomal RNA in nucleolar material properties, we degrade RNA using RNase A, which causes the DFC/FC to become more fluid-like and alters interfacial tension. Together, our findings suggest that RNA underlies the partially solid-like properties of the DFC/FC and provide insights into how material properties of nucleoli in a near-native environment are related to their RNA-dependent function.
    Keywords:  biomolecular condensates; nucleolus; organelles; rheology; soft matter
    DOI:  https://doi.org/10.1073/pnas.2407423122
  4. Development. 2025 May 30. pii: dev.204674. [Epub ahead of print]
    A sperm-oocyte protein partnership required for egg activation in Caenorhabditis elegans.
    Tatsuya Tsukamoto, Ji Kent Kwah, Mark E Zweifel, Naomi Courtemanche, Micah D Gearhart, Katherine M Walstrom, Aimee Jaramillo-Lambert, David Greenstein.
      Fertilization triggers the completion of female meiosis and launches the oocyte-to-embryo transition. C. elegans spe-11 is one of the few known paternal-effect embryonic lethal genes. We report that the sperm protein, SPE-11, forms a complex with an oocyte protein, OOPS-1 (Oocyte Partner of SPE-11) at fertilization, and that the protein complex is required for the completion of meiosis, the block to polyspermy, and eggshell formation. Consistent with the molecular interaction of their encoded proteins, oops-1 and spe-11 exhibit indistinguishable null phenotypes in which fertilized oocytes arrest in meiosis I or meiosis II or fail to complete the actin-based process of meiotic cytokinesis. Biochemical analysis shows that the complex binds F-actin in the absence of other proteins and inhibits the nucleation of actin filaments at substoichiometric concentrations. Both OOPS-1 and SPE-11 are intrinsically disordered proteins that are highly phosphorylated, and biochemical and genetic experiments define interactions with sperm-specific protein phosphatase 1 homologs GSP-3/4. Genetic results suggest that the cortical EGG complex recruits the OOPS-1-SPE-11 complex at fertilization, which promotes meiotic cytokinesis and in turn activates synthesis of the eggshell.
    Keywords:  And actin regulation; Egg activation; Fertilization; Meiotic cytokinesis; Oocyte meiosis
    DOI:  https://doi.org/10.1242/dev.204674
  5. Methods Mol Biol. 2025 ;2923 33-44
    Chromatin Analyses in Mouse Oocytes and Preimplantation Embryos.
    Zhiyuan Chen, Chunxia Zhang, Yi Zhang.
      Extensive chromatin reprogramming after fertilization is essential for successful zygotic genome activation (ZGA) and embryonic development. Traditional chromatin profiling techniques chromatin immunoprecipitation assay with sequencing (ChIP-seq) and deoxyribonuclease I hypersensitivity sequencing (DNase-seq) require large number of cells, which are not suitable for rare biological materials such as mammalian preimplantation embryos. Recent advancement of low-input epigenome profiling techniques has allowed the exploration of chromatin dynamics and functions during ZGA and early embryonic development. In this chapter, we describe two low-input methods, namely, CUT&RUN and ATAC-seq, that are efficient and robust for chromatin analyses using as few as 50-100 cells. These methods are useful for profiling histone modifications, histone variants, and chromatin accessibility in mammalian preimplantation studies.
    Keywords:  ATAC-seq; CUT&RUN; Chromatin; Low input; Oocytes; Preimplantation embryos
    DOI:  https://doi.org/10.1007/978-1-0716-4522-2_3
  6. Methods Mol Biol. 2025 ;2923 77-87
    CUT&Tag for Transcription Factor Binding Profiles During Mammalian Zygotic Genome Activation.
    Wataru Kobayashi, Kikuë Tachibana.
      Zygotic genome activation (ZGA) triggered by transcription factors (TFs) is a critical event to facilitate subsequent embryonic development. However, the paucity of material poses a challenge for mapping TF binding profiles in mammalian embryos. Here, we describe a low-input Cleavage Under Targets & Tagmentation (CUT&Tag) protocol optimized for TF binding using ~300 mouse two-cell embryos to investigate ZGA. This version of CUT&Tag is an immunostaining-based protocol with manual cell transfer by pipette to avoid loss of samples and gentle washing of fragile preimplantation embryos protected by the zona pellucida.
    Keywords:  CUT&Tag; Low-input sample; Mammalian preimplantation embryo; Transcription factor; Zygotic genome activation
    DOI:  https://doi.org/10.1007/978-1-0716-4522-2_6
  7. Methods Mol Biol. 2025 ;2923 181-194
    Monitoring miRNA Expression and Activity in Mammalian Oocytes and Early Embryos.
    Shubhangini Kataruka, Petr Svoboda.
      MicroRNAs (miRNAs), genome-encoded small RNAs associated with Argonaute proteins, are important negative regulators of gene expression in mammalian cells. miRNAs usually partially base pair with mRNAs, suppress their translation, and destabilize them. Sufficient miRNA abundance is an important factor for efficient target repression. Experimental evidence suggests that oocyte growth causes a dilution effect, which reduces concentrations of maternal miRNAs and renders them functionally inefficient. Consequently, efficient target repression is retained only by those maternal miRNAs which achieve a favorable miRNA:mRNA stoichiometry. Here, we provide protocols for PCR-based quantification of miRNAs and luciferase reporter-based analysis of their activity in mammalian oocytes and early embryos.
    Keywords:  Microinjection; NanoLuc; Oocyte; Zygote; mRNA reporter; miRNAs
    DOI:  https://doi.org/10.1007/978-1-0716-4522-2_11
  8. BMC Biol. 2025 May 28. 23(1): 147
    RNA multi-omics in single cells reveal rhythmical RNA reshaping during human and mouse oocyte maturation.
    Huan Yao, Danru Zhang, Haixia Jin, Yanjie Guo, Yan Liu, Shengnan Wang, Tong Li, Shenli Yuan, Gang Lu, Yingpu Sun.
       BACKGROUND: Omics technologies are widely applied in assisted reproductive technology (ART), such as embryo selection, investigation of infertility causes, and mechanisms underlying reproductive cell development. While RNAomics has shown great potential in investigating the physiology and pathology in female reproductive system, its applications are still not fully developed. More studies on epitranscriptomic regulation mechanisms and novel sequencing methods are needed to advance the field.
    RESULTS: Here, we developed a method named Cap to Tail sequencing application (C2T-APP) and simultaneously characterized the m7G cap, poly(A) tail structure, and gene expression level for the intact RNA molecules in single cells. C2T-APP distinguished the N6, 2'-O-dimethyladenosine modification (m6Am) from N6-methyladenosine (m6A) modification with our published single-cell m6A sequencing (scm6A-seq) data. During oocyte maturation, we found a positive correlation of m7G and m6Am with translation efficiency and finely dissected the step-wised maternal RNA de-capping and de-tailing of different types of genes. Strikingly, we uncovered a subtle structural mechanism regulating poly(A) tails in oocytes: maternal RNA translation is temporarily suppressed by removing the poly(A) tails without complete degradation, while the poly(A)-tail regulators themselves depend strictly on translation initiated after meiotic resumption. Furthermore, we profiled single-cell RNA-multi-omic features of human oocytes with different qualities during in vitro culture maturation (IVM). Defects of epi-transcriptome features, including m6A, m6Am, m7G, and poly(A) structure of maternal RNA in the oocytes with poor quality, were detected.
    CONCLUSIONS: Our results provided a valuable tool for RNAomics research and data resources provided novel insights into human oocyte maturation, which is helpful for IVM and oocyte selection for ART.
    Keywords:  Maternal RNA decay; Oocyte maturation; RNA modifications; RNA multi-omics in single cells; RNA terminal structure detection
    DOI:  https://doi.org/10.1186/s12915-025-02250-7
  9. Cell Biosci. 2025 May 24. 15(1): 68
    Role of ZBED3 in PALD1/PIP2- dependent calcium homeostasis during oocyte maturation.
    Danyu Ni, Qijun Xie, Yuting Chen, Yi Wei, Peng Lang, Xiaodan Shi, Ye Yang, Xiufeng Ling, Chun Zhao.
      Zinc Finger BED-Type Containing 3 (ZBED3) had been shown to be a novel component of the subcortical maternal complex (SCMC). In previous reports, ZBED3 depletion leads to asymmetric zygotic division and aberrant distribution of organelles in both oocytes and zygotes. However, the precise mechanism through which ZBED3 exerts its effects remains to be elucidated. To fill this gap, in this study, we generated Zbed3 gene knockout mice by using CRISPR/cas9 gene-editing technique to generate homozygous Zbed3-/- female mice. A series of previously unreported phenotypes in oocytes were observed, including decreased fertility, abnormal spindle formation and migration, increased polyspermic fertilization, abnormal distribution of cortical granules (CGs), and disrupted calcium oscillations. To investigate the molecular mechanisms underlying the function of ZBED3 during oocyte maturation, we employed miniTurbo biotin ligase-based proximity labeling combined with mass spectrometry to identify protein interactomes in transfected HEK293 cells. OF the 187 ZBED3-interacting proteins, paladin 1 containing a phosphatase domain (PALD1) and E3 ubiquitin ligase makorin-1 (MKRN1) exhibited the highest fold changes and were subsequently validated. ZEBD3 suppressed PALD1 levels by enhancing its degradation via the ubiquitination-proteasome pathway. Depletion of Zbed3 results in an abnormal accumulation of PALD1. The ectopic overexpression of PALD1 recapitulates the phenotypic defects observed in Zbed3-deficient oocytes and early embryos. Moreover, knockdown of PALD1 partially rescued the oocyte maturation defects induced by Zbed3 depletion. Paladin is an endosomal phosphatidylinositol 4,5-bisphosphate (PIP2) phosphatase which directly modulates phosphoinositide metabolism by catalyzing the removal of phosphate groups from phosphoinositides. Furthermore, PALD1 overexpression reduced Ca2+ release from the endoplasmic reticulum (ER) by inhibiting its downstream target PIP2. Our study demonstrates that ZBED3 may regulate PIP2 protein levels by modulating the ubiquitin-proteasomal degradation of PALD1, thereby influencing oocyte maturation and providing a novel approach for assessing oocyte quality and developmental potential.
    Keywords:  CRISPR/cas9; Calcium homeostasis; F-actin assembly; Oocyte maturation; PALD1; PIP2; Subcortical maternal complex (SCMC); ZBED3
    DOI:  https://doi.org/10.1186/s13578-025-01404-y
  10. Cells. 2025 05 12. pii: 696. [Epub ahead of print]14(10):
    Non-Redundant Essential Roles of Proteasomal Ubiquitin Receptors Rpn10 and Rpn13 in Germ Cell Formation and Fertility.
    Wan-Yu Yue, Yi Zhang, Tian-Xia Jiang, Xiao-Bo Qiu.
      Primordial germ cells (PGCs) undergo proliferation, migration, and sexual differentiation to produce gonocytes, which eventually generate germ cells. The proteasome, which degrades most cellular proteins, is a protein complex with dozens of subunits. The proteasomal ubiquitin receptors Rpn10 and Rpn13 have been shown to play partially overlapping roles in binding ubiquitin chains in vitro and in liver function in vivo. However, the specific role of Rpn10 and Rpn13 in germ cell production remains unclear. We show here that Rpn10 and Rpn13 are each essential for germ cell production and fertility. The conditional deletion of either Rpn10 or Rpn13 in PGCs results in infertility in both male and female mice. Germ cells in testes and ovaries all decreased dramatically in the Rpn13 conditional knockout (cKO) mice. Specifically, the deletion of Rpn13 in PGCs disrupts the assembly of the 26S proteasome, reduces the number of PGCs, and blocks the meiosis of spermatocytes at the zygotene stage during prophase I; on the other hand, the deletion of Rpn10 in PGCs sharply reduces PGC migration. These results are important for understanding the roles of Rpn10 and Rpn13 in germ cell development and related reproductive diseases.
    Keywords:  Rpn10; Rpn13; fertility; oogenesis; primordial germ cell; proteasome; spermatogenesis; ubiquitin
    DOI:  https://doi.org/10.3390/cells14100696
  11. Cells. 2025 05 12. pii: 704. [Epub ahead of print]14(10):
    Transcriptomic Profile of Early Antral Follicles: Predictive Somatic Gene Markers of Oocyte Maturation Outcome.
    Alessia Peserico, Barbara Barboni, Chiara Camerano Spelta Rapini, Chiara Di Berardino, Giulia Capacchietti, Angelo Canciello, Fani Konstantinidou, Marisa Donato, Liborio Stuppia, Valentina Gatta.
      Early antral follicles (EAfs) offer oocyte potential in Assisted Reproductive Technology (ART), but most fail to mature under current in vitro maturation (IVM) protocols. This study examines transcriptomic profiles of the follicular wall (FW) compartment during IVM in ovine EAfs using a 3D follicle-enclosed oocyte (FEO) culture to identify somatic gene markers predicting oocyte maturation success. Differentially expressed genes (DEGs) were identified across three comparisons: pre- vs. post-hCG in FW enclosing mature/fertilizable (1) or immature (2) oocytes, and post-hCG between FW supporting successful vs. failed maturation (3). Network analysis highlighted key modulated and HUB genes. Two DEG categories emerged: genes regulating meiosis resumption and genes defining follicular signatures linked to oocyte competence. Meiosis resumption involved ECM remodeling, hypoxia, and relaxin signaling activation, while proliferative and metabolic pathways were downregulated. MMP13 and EGFR regulated the ECM pathway, working for meiosis resumption, while TGFB1 predicted failure. Oocyte competence involves ECM activation and the suppression of stress and cell cycle pathways, with ITIH4 being conducive to central HUB tuning inflammation and angiogenesis-dependent maturation. This study reveals molecular mechanisms behind follicle maturation, identifying transcriptomic signatures for FW releasing mature/fertilizable and incompetent oocytes. It confirms known biomarkers and uncovers new regulators, offering tools to assess follicle quality, improve IVF-oocyte selection, and enhance fertility preservation.
    Keywords:  IVF; driver genes; follicle biomarkers; follicle-enclosed oocyte maturation; oocyte quality; transcriptomic profile
    DOI:  https://doi.org/10.3390/cells14100704
  12. Methods Mol Biol. 2025 ;2923 143-162
    Quantifying Nascent Transcription in Early Embryogenesis.
    Hui Chen.
      The early embryonic genome exists in a dormant state following fertilization, and it then subsequently undergoes broad activation of zygotic transcription at the early stages of development. A major challenge is the detection of newly made zygotic transcripts and the determination of their activation onset time due to the presence of large and predominantly maternal pool of RNAs. Here we describe a detailed method to measure the zygotic transcription during zygotic genome activation (ZGA) of Xenopus early embryos using metabolic labeling of nascent transcripts with 5-ethynyl uridine (5-EU) followed by purifying and sequencing the nascent EU-RNAs (EU-RNA-seq). This method is highly sensitive in detecting early zygotic transcripts that are not detected by total RNA-seq and determines the actual onset time of transcriptional activation for zygotic genes. The method is applicable to a wide variety of embryonic model systems and has already afforded novel insights into gene regulation in early embryogenesis.
    Keywords:  5-ethynyl uridine (5-EU); Early embryogenesis; Nascent transcription; RNA sequencing (RNA-seq); Transcriptome; Zygotic genome activation
    DOI:  https://doi.org/10.1007/978-1-0716-4522-2_9
  13. FASEB J. 2025 Jun 15. 39(11): e70662
    Functional Characterization and Heterogeneity Analysis of Ribosomal Proteins in Mouse Preimplantation Embryos.
    Seung Jae Lee, Dayeon Kim, Gwidong Han, Seung Pyo Hong, Inchul Choi, Chunghee Cho.
      Translational control is important during the mammalian preimplantation phase, when maternal RNAs and proteins are degraded and de novo synthesis of RNAs and proteins increases. Proteins are synthesized in ribosomes, which are assembled from ~82 ribosomal proteins (RPs). The function of ribosomes varies depending on the resident RPs, suggesting that ribosome heterogeneity can lead to functional specialization. Only a few studies have investigated the function of RPs during preimplantation embryonic development. Here, we performed functional analyses on six RP-encoding genes-Rpl4, Rps9, Rps11, Rpl13a, Rpl19, and Rpl39-in mouse preimplantation embryos. Knockdown (KD) of each of these RP genes, except Rpl39, affected morula-to-blastocyst transition, producing phenotypes that varied somewhat in their details. Rpl4-, Rpl13a-, and Rpl19-KD embryos showed fragmentation and strong arrest of cell proliferation, whereas Rps9- and Rps11-KD embryos showed severe fragmentation with relatively weak arrest of cell proliferation. In the case of Rpl39, single-KD embryos developed normally, but double-KD embryos with its paralog Rpl39-like (Rpl39l) inhibited normal blastocyst development. Protein misfolding signals were also activated in Rpl39-KD and Rpl39l + Rpl39 double-KD embryos, confirming a previous finding that RPL39 and RPL39L are associated with ribosome exit tunnels. Our results suggest the presence of different groups of proteins that require an RPL39-containing ribosome or RPL39/RPL39L-containing ribosome for correct folding in early embryos. Taken together, the results of the present study demonstrate that ribosomal proteins are fundamentally important for normal blastocyst formation and development, but not all ribosomal proteins contribute equally to embryonic development, providing a novel example of ribosome heterogeneity in preimplantation embryos.
    Keywords:  de novo protein synthesis; morula to blastocyst transition; mouse preimplantation embryo; protein folding; ribosomal protein; ribosome heterogeneity
    DOI:  https://doi.org/10.1096/fj.202500574RR
  14. Sci Adv. 2025 May 30. 11(22): eadu8572
    Notch controls APC/CFZR-1 to enable accumulation of chromatin regulators in germline stem cells from Caenorhabditis elegans.
    David Puerta, Sara Rivera-Martín, Adrián Fragoso-Luna, Susan Strome, Sarah L Crittenden, Judith Kimble, José Pérez-Martín.
      Originally known for its function in the cell cycle, the anaphase-promoting complex/cyclosome (APC/C) also plays a crucial role in regulating differentiation and maintaining cell identity. However, the mechanisms by which APC/C mediates developmental processes are not fully understood. In this study, we show that APC/C and its activator FZR-1 regulate the chromatin regulators MES-4 and MES-3. These proteins are part of histone methylation complexes essential for maintaining germline stem cell (GSC) identity in the germ line of Caenorhabditis elegans. APC/CFZR-1 facilitates the degradation of MES-4 and MES-3 when GSCs transition toward differentiating into oocytes. The activity of APC/CFZR-1 is restricted by the Notch signaling pathway provided by the distal tip cell, which is responsible for maintaining the stemness of the GSC pool. This negative regulation enables the accumulation of MES-3 and MES-4 in GSCs, offering an additional component by which niche activity modulates the C. elegans germ line.
    DOI:  https://doi.org/10.1126/sciadv.adu8572
  15. J Cell Biol. 2025 Aug 04. pii: e202411073. [Epub ahead of print]224(8):
    Ecdysone regulates phagocytic cell fate of epithelial cells in developing Drosophila eggs.
    Gaurab Ghosh, Devyan Das, Abhrajyoti Nandi, Souvik De, Sreeramaiah N Gangappa, Mohit Prasad.
      Acquisition of nonprofessional phagocytic cell fate plays an important role in sculpting functional metazoan organs and maintaining overall tissue homeostasis. Though physiologically highly relevant, how the normal epithelial cells acquire phagocytic fate is still mostly unclear. We have employed the Drosophila ovary model to demonstrate that the classical ecdysone signaling in the somatic epithelial follicle cells (AFCs) aids the removal of germline nurse cells (NCs) in late oogenesis. Our live-cell imaging data reveal a novel phenomenon wherein collective behavior of 4-5 AFCs is required for clearing a single NC. By employing classical genetics, molecular biology, and yeast one-hybrid assay, we demonstrate that ecdysone modulates the phagocytic disposition of AFCs at two levels. It regulates the epithelial-mesenchymal transition of the AFCs through Serpent and modulates the phagocytic behavior of the AFCs through Croquemort and Draper. Our data provide unprecedented novel molecular insights into how ecdysone signaling reprograms AFCs toward a phagocytic fate.
    DOI:  https://doi.org/10.1083/jcb.202411073
  16. Proc Natl Acad Sci U S A. 2025 Jun 03. 122(22): e2411964122
    Transcription-templated assembly of the nucleolus in the Caenorhabditis elegans embryo.
    Nishant Kodan, Rabeya Hussaini, Stephanie C Weber, Jane Kondev, Lishibanya Mohapatra.
      The nucleolus is a multicomponent structure made of RNA and proteins that serves as the site of ribosome biogenesis within the nucleus. It has been extensively studied as a prototype of a biomolecular condensate whose assembly is driven by phase separation. While the steady-state size of the nucleolus is quantitatively accounted for by the thermodynamics of phase separation, we show that experimental measurements of the assembly dynamics are inconsistent with a simple model of a phase-separating system relaxing to its equilibrium state. Instead, we show that the dynamics are well described by a model in which the transcription of ribosomal RNA actively drives nucleolar assembly. We find that our model of active transcription-templated assembly quantitatively accounts for the rapid kinetics observed in early embryos at different developmental stages, and for different RNA interference (RNAi) perturbations of embryo size. Our model predicts a scaling of the time to assembly with the volume of the nucleus to the one-third power, which is confirmed by experimental data. Our study highlights the role of active processes such as transcription in controlling the placement and timing of assembly of membraneless organelles.
    Keywords:  membraneless organelles; nucleolar assembly; transcription-templated assembly
    DOI:  https://doi.org/10.1073/pnas.2411964122
  17. Aging (Albany NY). 2025 May 20. 17
    Short-term moderate caloric restriction in the rhesus macaque attenuates markers of ovarian aging in select populations.
    Emma S Gargus, Rhea Sharma, Rebecca Gu, Camille Mulcahy, Brian W Johnson, Jing Song, Jungwha Lee, Mary Zelinski, Francesca E Duncan.
      Ovarian aging results in decreased fertility and endocrine function. In mice, caloric restriction (CR) maintains ovarian function. In this study, we determined whether CR also has a beneficial effect on reproductive longevity in the nonhuman primate (NHP). Ovaries were collected from young (10-13 years) and old (19-26 years) rhesus macaques who were either on a diet of moderate caloric restriction or a control diet for three years. To test the effect of CR on follicle number, follicles were analyzed in histological sections from animals across experimental cohorts: Young Control, Young CR, Old Control, Old CR (n = 4-8/group). In control animals, there was an age-dependent decrease in follicle numbers across all follicle stages (P < 0.05). Although there was no effect of diet on total follicle number, the follicle distribution in the Old CR cohort more closely resembled that of young animals. The subset of Old CR animals that were still cycling, albeit irregularly, had more primordial follicles than controls (P < 0.05). Assessment of collagen and hyaluronic acid matrices revealed that CR attenuated age-related changes to the ovarian microenvironment. Overall, CR may improve aspects of reproductive longevity in the NHP, but the timing of when it occurs during the reproductive lifespan is likely critical.
    Keywords:  aging; caloric restriction; fibrosis; nonhuman primate; ovarian reserve
    DOI:  https://doi.org/10.18632/aging.206253
  18. Mol Cell. 2025 May 22. pii: S1097-2765(25)00414-9. [Epub ahead of print]
    Catalytic-dependent and independent functions of the histone acetyltransferase CBP promote pioneer-factor-mediated zygotic genome activation.
    Audrey J Marsh, Sergei Pirogov, Yadwinder Kaur, Abby J Ruffridge, Suresh Sajwan, Tyler J Gibson, George Hunt, Melissa M Harrison, Mattias Mannervik.
      Immediately after fertilization, the genome is transcriptionally quiescent. Maternally encoded pioneer factors reprogram the chromatin state and facilitate transcription of the zygotic genome. In Drosophila, transcription is initiated by the pioneer factor Zelda. While Zelda-occupied sites are enriched with histone acetylation, a post-translational mark associated with active cis-regulatory regions, the functional relationship between Zelda and histone acetylation remained unclear. We show that Zelda-mediated recruitment of the histone acetyltransferase CREB-binding protein (CBP) is essential for zygotic transcription. CBP catalytic activity is necessary for the release of RNA polymerase II (RNA Pol II) into elongation and for embryonic development. However, CBP also activates transcription independent of acetylation through RNA Pol II recruitment. Neither CBP-mediated acetylation nor CBP itself is required for the pioneering function of Zelda. Our data suggest that pioneer-factor-mediated recruitment of CBP is a conserved mechanism required to activate zygotic transcription but is separable from the function of pioneer factors in restructuring chromatin accessibility.
    Keywords:  Drosophila; RNA polymerase; histone acetyltransferase; pioneer factor; transcription; zygotic genome activation
    DOI:  https://doi.org/10.1016/j.molcel.2025.05.009
  19. Nat Commun. 2025 May 24. 16(1): 4828
    hnRNPL phase separation activates PIK3CB transcription and promotes glycolysis in ovarian cancer.
    Fengjiang Qin, Yuya Wang, Chenyue Yang, Yifei Ren, Qinglv Wei, Yan Tang, Jie Xu, Haocheng Wang, Fatao Luo, Qingya Luo, Xin Luo, Xiaoyi Liu, Dan Yang, Xinzhao Zuo, Yu Yang, Chunming Cheng, Jing Xu, Wei Wang, Tao Liu, Ping Yi.
      Ovarian cancer has the highest mortality rate among gynecologic tumors worldwide, with unclear underlying mechanisms of pathogenesis. RNA-binding proteins (RBPs) primarily direct post-transcriptional regulation through modulating RNA metabolism. Recent evidence demonstrates that RBPs are also implicated in transcriptional control. However, the role and mechanism of RBP-mediated transcriptional regulation in tumorigenesis remain largely unexplored. Here, we show that the RBP heterogeneous ribonucleoprotein L (hnRNPL) interacts with chromatin and regulates gene transcription by forming phase-separated condensates in ovarian cancer. hnRNPL phase separation activates PIK3CB transcription and glycolysis, thus promoting ovarian cancer progression. Notably, we observe that the PIK3CB promoter is transcribed to produce a non-coding RNA which interacts with hnRNPL and promotes hnRNPL condensation. Furthermore, hnRNPL is significantly amplified in ovarian cancer, and its high expression predicts poor prognosis for ovarian cancer patients. By using cell-derived xenograft and patient-derived organoid models, we show that hnRNPL knockdown suppresses ovarian tumorigenesis. Together, our study reveals that phase separation of the chromatin-associated RBP hnRNPL promotes PIK3CB transcription and glycolysis to facilitate tumorigenesis in ovarian cancer. The formed hnRNPL-PIK3CB-AKT axis depending on phase separation can serve as a potential therapeutic target for ovarian cancer.
    DOI:  https://doi.org/10.1038/s41467-025-60115-7
  20. Am J Physiol Cell Physiol. 2025 May 28.
    The role of KAT6A in regulating primordial follicle activation in mouse ovary.
    Yan Zhang, Xiaoran Nie, Liu Yang, Tuo Zhang, Jixian Zhang, Xiaojing Yang, Yanhua Yang, Chunlin Zhang, Meina He.
      Follicle is a primary structural and functional unit within the mammalian ovary, encompassing a centrally positioned oocyte surrounded by pre-granulosa cells. Primordial follicles constitute the ovarian reserve, the activated primary follicle represents the inception of follicular development in mammals. The intricate balance between primordial follicle dormancy and activation is pivotal for sustaining ovarian reproductive function; over-activation of the primordial follicle pool can result in premature ovarian failure among women. Although recent studies have revealed that several functional genes and pathways, such as mTOR signaling, play roles in controlling the activation of primordial follicles, our understanding of the molecular networks regulating the activation progress is still incomplete. Here, using the mouse in vitro ovarian culture model, we identify a new role for K (lysine) acetyltransferase 6A (KAT6A) in regulating the activation of primordial follicles in mice. Our results show that the expression of KAT6A is increased during primordial follicle activation in the oocytes. Disruption of KAT6A activity with two specific inhibitors significantly suppresses primordial follicle activation in cultured mouse ovaries. Furthermore, we find that KAT6A regulates P-body signaling pathway and the expression levels of Ddx6 in oocytes. This suggests that KAT6A may promote primordial follicle activation by regulating the P-body signaling pathway. Collectively, our results elucidate that KAT6A plays a crucial role in controlling the activation of primordial follicles in the mammalian ovary.
    Keywords:  KAT6A; P-body; mTOR signaling pathway; primordial follicle activation
    DOI:  https://doi.org/10.1152/ajpcell.00055.2025
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