bims-cebooc 2026-04-19 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–04–19
ten papers selected by
Gabriele Zaffagnini, Universität zu Köln

Cytoplasmic lattices are megadalton storage complexes in mammalian oocytes.
H2AK119ub1-MLL2 counteraction underlies heritable H3K27me3 formation in oocytes.
Probing Proteoform Heterogeneity from Single Human Oocytes.
Outer kinetochore proteins form linear elements to regulate vesicle transport.
Metabolic Labeling of the Nascent Transcriptome in Xenopus Early Embryogenesis.
Stn1 promotes zebrafish oocyte development via amplifying Wnt/β-catenin signaling.
Roles and Regulation of the Hippo Signaling Pathway in Mammalian Preimplantation Development.
The transcription factor LSL-1 interacts with the chromatin factors HIM-17, XND-1 and BRA-2 to promote the germline-specific transcriptional repertoire and to safeguard germ cell fate in C. elegans.
The dynamic evolution of panarthropod germ cell specification mechanisms.
A trans -piRNA network and transcriptional antagonism shape piRNA cluster function.

Nature. 2026 Apr 15.

Cytoplasmic lattices are megadalton storage complexes in mammalian oocytes.

Zeynep Ilgın Kılıç, Joyce van Loenhout, Marten Chaillet, Robert M van Es, Paula Sobrevals Alcaraz, Harmjan R Vos, Willem E M Noteborn, Miguel Ricardo Leung.

Mammalian oocytes store proteins for embryonic development on abundant structures known as cytoplasmic lattices (CPLs)1; however, the mechanisms by which they achieve this are unclear, largely because the molecular composition of the lattices themselves is unknown. Here, we use cryo-electron microscopy and artificial intelligence-based modeling to elucidate the molecular architecture and protein composition of native CPLs from mouse oocytes. We find that CPLs are formed by at least 13 different proteins assembling into a megadalton-scale complex, including multiple copies of maternal effect factors such as PADI6 and the subcortical maternal complex (SCMC). We show that proteins essential for early embryonic development are in fact structural components of the CPLs, including the cytoskeletal proteins α- and β-tubulin, which are incorporated into CPLs as unpolymerized dimers; and an array of ubiquitination factors such as the epigenetic regulator and E3 ligase UHRF1, ubiquitin-conjugating E2 enzymes, and ubiquitin ligase substrate adaptors. This represents an elegant molecular mechanism by which oocytes stockpile vital proteins through direct incorporation into highly stable supramolecular assemblies. Our structures solve the decades-long mystery of the CPLs, thereby providing a structural framework for understanding how disrupting stored maternal factors leads to infertility and developmental defects.

DOI: https://doi.org/10.1038/s41586-026-10513-8
Mol Cell. 2026 Apr 13. pii: S1097-2765(26)00190-5. [Epub ahead of print]

H2AK119ub1-MLL2 counteraction underlies heritable H3K27me3 formation in oocytes.

Hailiang Mei, Chisayo Kozuka, Mami Kumon, Haruhiko Koseki, Azusa Inoue.

  Polycomb group (PcG) and Trithorax group (TrxG) proteins establish bivalent chromatin marked by H3K27me3, H2AK119ub1, and H3K4me3. However, how bivalent chromatin is formed in vivo in mammals is poorly understood. In mouse oocytes, it arises at thousands of promoters, including noncanonical imprinted loci whose H3K27me3 is intergenerationally inherited by early embryos. Here, we show that H3K27me3 is deposited at H3K4me3-premarked promoters in an H2AK119ub1-dependent manner during oogenesis. We find that H2AK119ub1 deficiency causes transcriptional derepression and loss of H3K27me3 proportional to preexisting H3K4me3 levels in oocytes. Importantly, concomitant deficiency of H2AK119ub1 and MLL2-mediated H3K4me3 substantially restores transcriptional silencing and H3K27me3 deposition, leading to partial restoration of noncanonical imprinting in offspring. Taken together, we propose that H2AK119ub1 antagonizes MLL2 function to repress bivalent genes during oogenesis, thereby conferring heritable H3K27me3. This study reveals how PcG and TrxG counteraction shapes the maternal epigenome for the next generation's development.

Keywords:  MLL2; Polycomb; Trithorax; bivalent chromatin; epigenetic inheritance; genomic imprinting; mouse oocyte; placenta

DOI:  https://doi.org/10.1016/j.molcel.2026.03.014
Mol Cell Proteomics. 2026 Apr 09. pii: S1535-9476(26)00062-9. [Epub ahead of print] 101566

Probing Proteoform Heterogeneity from Single Human Oocytes.

Nickolas P Fisher, Vijaya Lakshmi Kanchustambham, Elizabeth L Tsui, Chelsea Lock, Tian Xu, Hannah B McDowell, Indira Pla, Diane C Saunders, Jared O Kafader, Monica M Laronda, Neil L Kelleher.

Ovarian tissue cryopreservation (OTC) is a fertility preservation strategy available to prepubertal patients undergoing gonadotoxic treatment who are at risk of developing premature ovarian insufficiency or for those whose treatment cannot be delayed. While cryopreserved tissue can be utilized for ovarian tissue transplantation (OTT) to restore hormone function and fertility in some of these individuals, those with a high risk of malignant cell reintroduction currently have no options. In vitro Maturation (IVM) of isolated immature oocytes from prepubertal patients is not yet successful enough for the clinic, necessitating study of the molecular factors influencing oocyte quality for IVM success. In this study, we characterized intact proteoforms from single human oocytes obtained from OTC and tissue donation in a donor cohort aged 2-33 years old to identify changes in the oocyte proteome across the pubertal transition. Utilizing single cell proteoform imaging mass spectrometry (scPiMS), which employs a sampling probe to raster over single cells coupled to individual ion mass spectrometry (I2MS) detection, we identified 559 proteins and 769 unique proteoforms across 28 oocytes from 8 donors, with an average of 78 unique proteoforms per oocyte. We used scPiMS to selectively sample oocytes and cumulus granulosa cells from single cumulus oocyte complexes (COCs) to identify proteoforms specific to these cell types. Finally, we determined proteoform landscapes for members of the oocyte-specific subcortical maternal complex (SCMC), KHDC3 and OOEP, and found new proteoforms that differ with donor age. Together, these first-in-class observations provide a foundation for understanding protein-level changes in oocyte biology across puberty to ultimately improve the efficiency of IVM and make fertility restoration options accessible for more patients.

DOI: https://doi.org/10.1016/j.mcpro.2026.101566
J Cell Sci. 2026 Apr 13. pii: jcs.264478. [Epub ahead of print]

Outer kinetochore proteins form linear elements to regulate vesicle transport.

Shane J Kowaleski, Alexis Bridgewater, Cody Saraceno, Miranda Dudek, Federico Pelisch, Joshua N Bembenek.

  During cell division, several key regulators of chromosome segregation play additional roles during vesicle trafficking required for cytokinesis. During anaphase I in C. elegans oocytes, chromosome segregation is coordinated with vesicle trafficking to support polar body extrusion and exocytosis of extracellular matrix material. Prior to anaphase, numerous outer kinetochore proteins localize to mysterious "linear element" structures throughout the cortex in addition to chromosomes, which has been observed in oocytes of multiple species. Here, we demonstrate that linear elements initially form as puncta just before nuclear envelope breakdown and rapidly assemble into larger elongated structures. As linear elements grow, they form large clusters with cortical granule secretory vesicles, initiating an elaborate transport mechanism that distributes vesicles throughout the cortex by anaphase I. Linear elements dynamically interact with microtubules and endoplasmic reticulum during this process. Microtubules are required for linear element assembly, motility, and vesicle transport. Knockdown of a plus-end microtubule-binding kinetochore component also inhibits linear element growth and vesicle clustering, but not the motility of linear element puncta. Depletion of several outer kinetochore proteins causes defects in extracellular matrix formation. Therefore, linear elements facilitate the microtubule-dependent transport of vesicles for their proper distribution in the cortex, which is essential for oocyte development.

Keywords:  Linear Element; Oocyte; Outer Kinetochore; Vesicle transport

DOI:  https://doi.org/10.1242/jcs.264478
J Vis Exp. 2026 Mar 27.

Metabolic Labeling of the Nascent Transcriptome in Xenopus Early Embryogenesis.

Chuan Qin, Hui Chen.

Early embryogenesis requires new transcription of zygotic genes from the initially dormant zygotic genome after fertilization. A major challenge has been to accurately detect the new transcripts and determine their time of expression during zygotic genome activation (ZGA). Here, we provide detailed procedures for metabolic labeling of the nascent transcripts by 5-ethynyl-uridine (5-EU) in early Xenopus laevis embryos. After fertilization, 5-EU is microinjected into the 1-cell stage embryos to metabolically label the newly transcribed RNAs during ZGA. The nascent EU-RNAs are subsequently purified after biotinylation via click chemistry-mediated reactions, and the nascent transcriptome is determined using next-generation sequencing. Importantly, this method has high sensitivity and specificity that allow the characterization of lowly activated genes. Thus, this approach provides a powerful tool to study the dynamics of gene transcription during early development, and it can be generalized to other embryonic systems or tissues.

DOI: https://doi.org/10.3791/70591
EMBO Rep. 2026 Apr 17.

Stn1 promotes zebrafish oocyte development via amplifying Wnt/β-catenin signaling.

Xin Zhang, Yanpeng Zhai, Caixia Wang, Yuxue He, Yuxin He, Bo Wang, Chensong Huang, Aibo Sheng, Yan Bai, Xiaozhi Rong, Jianfeng Zhou.

Wnt/β-catenin signaling regulates oocyte development in vertebrates. However, the dynamics of Wnt/β-catenin signaling in oocyte progression remain unclear. Here, we analyze oocytes across different developmental stages in zebrafish and find that the activity of Wnt/β-catenin signaling sharply increases when oocytes reach a size of 10 to 45 μm (stage IA to middle stage IB) and subsequently declines rapidly. In addition, we show that expression of the CST complex subunit Stn1 is enriched in germ cells. Stn1 interacts with the transcription factor Tcf/Lef, facilitates its association with promoters of germ cell-specific genes, thereby enhancing Wnt/β-catenin signaling activity in oocytes. Genetic deletion of stn1 leads to massive loss of oocytes prior to or during their development to stage IB, resulting in a male-like phenotype associated with infertility. Temporal activation of the Wnt/β-catenin signaling pathway partially restores germ cell loss and facilitates oocyte development to stage IB. Our findings highlight the importance of Wnt/β-catenin signaling in promoting the expression of germ cell-specific genes and provide novel insights into the physiological function of Stn1 in maintaining oocyte development in zebrafish.

DOI: https://doi.org/10.1038/s44319-026-00775-8
Cold Spring Harb Perspect Biol. 2026 Apr 17. pii: a041908. [Epub ahead of print]

Roles and Regulation of the Hippo Signaling Pathway in Mammalian Preimplantation Development.

Hiroshi Sasaki.

During preimplantation development, mammalian embryos form blastocysts. Studies in mouse embryos have revealed multiple roles of the Hippo signaling pathway in this process. Among them, the process of TEA domain transcription factor 4 (TEAD4)-Yes-associated protein (YAP) control of trophectoderm (TE) and inner cell mass fate is the most extensively characterized. The major mechanism of YAP regulation is the activation of Hippo signaling by adherens junctions and inhibition by cell polarization or the apical domain. Several additional mechanisms further modulate Hippo signaling and/or YAP, including polarity regulation by Rho-associated coiled-coil-containing protein kinase (ROCK) and transcription factor AP-2γ (TFAP2C), angiomotin (AMOT) regulation by Ras homolog (RHO), asymmetric inheritance of the apical domain, mechanical regulation, and glucose metabolism. Hippo signaling also regulates other processes during embryogenesis, including zygotic gene activation by maternal YAP, cell state transition at the 8-cell stage, and maturation and quality control of the epiblast via cell competition. The TE fate regulatory role of the Hippo pathway is evolutionarily conserved among mammalian species, including human and bovine embryos, but some details differ.

DOI: https://doi.org/10.1101/cshperspect.a041908
bioRxiv. 2026 Apr 07. pii: 2026.04.05.716469. [Epub ahead of print]

The transcription factor LSL-1 interacts with the chromatin factors HIM-17, XND-1 and BRA-2 to promote the germline-specific transcriptional repertoire and to safeguard germ cell fate in C. elegans.

Magali Nanchen, David Rodriguez Crespo, Michael Stumpe, Chantal Wicky.

Germ cells are the only cells of an organism that pass onto the next generation and, hence perpetuate the species. To ensure this, germ cells need dedicated transcriptional repertoire, that ensure specification, proliferation, differentiation and fate maintenance. We previously characterized LSL-1, a conserved zinc-finger transcription factor that acts as a major direct transcriptional activator of genes involved in germ cell development, fate specification, meiosis and genome stability. Here, we show that LSL-1 interacts with the transcription factor HIM-17, the chromatin proteins BRA-2 and XND-1. These proteins are functionally related to LSL-1 and they colocalize at germline gene promoters, forming most likely a transcription-promoting complex. Furthermore, LSL-1 lies in close proximity to members of the COMPASS and the MOF complexes, corroborating the observation that HIM-17 and LSL-1 are required to maintain normal level of H3K4 methylation in the gonad. Finally, we show that LSL-1 interacting partners are necessary to maintain germ cell fate. Altogether, we propose that LSL-1 interacts with transcription regulators and chromatin modifiers to ensure the establishment of the transcriptional repertoire appropriate for germline function as well as for cell fate maintenance.

DOI: https://doi.org/10.64898/2026.04.05.716469
Development. 2026 Apr 01. pii: dev205168. [Epub ahead of print]153(7):

The dynamic evolution of panarthropod germ cell specification mechanisms.

Jonchee A Kao, Emily L Rivard, Rishabh R Kapoor, Cassandra G Extavour.

  Germ cells enable the reproduction of an organism and the continuity of its lineage. Across animals, these crucial cells are segregated from the soma at different times and places and via distinct mechanisms. Understanding the evolution of germ cell specification across animals is complicated by the difficulty of making meaningful comparisons of embryonic development between diverse animal species. Here, we characterize germ cell specification in Panarthropoda, an ancient clade that encompasses massive animal biodiversity, within which we can conduct meaningful comparative embryology. We amass data from centuries of studies describing the timing and mechanisms of germ cell formation, and apply ancestral state reconstruction to these data to propose hypotheses about the trajectory of evolution in this process. Furthermore, we speculate about the mechanisms underlying these evolutionary dynamics by considering the relationships among germ cell specification, concurrent developmental processes and the germ line gene network. Collectively, this Review derives new insights from a rich historical database of embryological observations, offering broad implications for understanding the evolution of metazoan germ cells.

Keywords:  BMP signaling pathway; Cytoplasmic determinant; Germ plasm; Inductive signaling; Pole cells

DOI:  https://doi.org/10.1242/dev.205168
bioRxiv. 2026 Apr 09. pii: 2026.04.08.717276. [Epub ahead of print]

A trans -piRNA network and transcriptional antagonism shape piRNA cluster function.

Yicheng Luo, Daniel Siqueira de Oliveira, Peng He, Alexei A Aravin.

PIWI-interacting (pi)RNAs protect animal germlines from transposable elements (TEs) by guiding their sequence-specific repression. In Drosophila germline, piRNAs are encoded in distinct genomic regions, piRNA clusters (piCs), that are transcribed by a non-canonical machinery that is anchored on chromatin by the HP1 paralogue Rhino. Studies of transgenic piCs revealed that piRNA biogenesis depends on cytoplasmic inheritance of piRNAs, however, whether native piCs require trans-generational piRNA transmission remained unknown. Here, we used two approaches to show that cytoplasmic inheritance of cognate piRNAs is critical for piRNA biogenesis. Our analyses reveal that individual piCs form a tightly interconnected network linked by trans -acting piRNAs that reinforce biogenesis. According to the transposon trap model, the content of piCs is updated by integration of novel TEs leading to production of piRNA guides against integrated transposons. However, we found that transcription driven by promoters integrated into piCs disrupt local piRNA biogenesis by removing Rhino and antagonizing non-canonical transcription of piRNA precursors. Thus, newly inserted transposons might suppress piRNA production before they become domesticated by the piRNA pathway calling for a revision of the trap model. Together, our results reveal that piC activity is shaped by transcriptional competition and a dynamic interplay between individual piCs connected into a common network.
Highlights: Cytoplasmic inheritance of maternal piRNAs is required for piRNA biogenesis in the next generation Trans -acting piRNA ensure robustness of piRNA biogenesis and repression by connecting individual clusters into a functional network Ping-pong amplification provides non-uniform processing of different regions inside piCsGenes can remain active inside piRNA clusters antagonizing Rhino-dependent non-canonical transcription and piRNA biogenesis, challenging the transposon trap model.

DOI: https://doi.org/10.64898/2026.04.08.717276