bims-cebooc 2026-11-15 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–11–15
six papers selected by
Gabriele Zaffagnini, Universität zu Köln

Transient nuclear softening for zygotic gene activation in mice.
Reciprocal constraints couple architectural protein abundance and pericentromeric satellite expansion.
Transcription factor 3 cooperates with CXXC finger protein 1 to regulate histone H3K4 trimethylation and developmental competence in mouse oocytes.
SCAN-seq2 reveals mitochondrial metabolic alterations and proteostasis-related transcriptional signatures during human oocyte aging.
Label-free imaging reveals lipid droplet dynamics during mouse preimplantation development.
Unilateral gene expression via maternally controlled zygotic recombination in Drosophila.

Nature. 2026 Nov 11.

Transient nuclear softening for zygotic gene activation in mice.

Masahito Tanaka, Rin Sakanoue, Yasuki Miyagawa, Kai Otsuka, Yoshiaki Kobayashi, Atsushi Takasu, Ryunosuke Mori, Naoko Watanabe, Akihiro Inoue, Koyo Ikeda, Yu-Chia Chen, Aussie Suzuki, Yasuyuki Ohkawa, So Maezawa, Hiroshi Ochiai, Kei Miyamoto, Yuta Shimamoto.

Nuclei in early mammalian embryos undergo epigenetic reprogramming that enables the zygote to develop into a complete organism. Whereas changes in chromatin state during this critical transition period have been extensively studied1-3, changes in the nucleus that houses chromatin remain poorly understood. Here, using direct organelle capture and biophysical manipulation methods, we find that nuclei attain profound softness and plasticity during the two-cell embryonic stage in mice, facilitating major zygotic gene activation. The prominent nuclear deformability is attributable to the rapid clearance of lamin B1 from the nuclear envelope by the autophagy factor LC3. Nuclear stiffening by lamin B1 retention or its overloading results in incomplete activation of zygotic genes and impaired development. However, embryos that maintain nuclear deformability escape from this transcriptional interference. High-resolution microscopy and sequential three-dimensional fluorescence in situ hybridization analyses revealed an accumulation of active RNA polymerase II and coordinated positioning of key genomic loci near the deformable nuclear envelope. An engineered molecular tether that stiffens the nuclei restricts these nuclear activities and suppresses expression of key zygotic gene activation genes. Together, our study identifies a distinct physical nuclear state that embryos acquire at the beginning of life that supports the initiation of the zygotic transcription program.

DOI: https://doi.org/10.1038/s41586-026-11240-w
Curr Biol. 2026 Nov 10. pii: S0960-9822(26)01426-0. [Epub ahead of print]

Reciprocal constraints couple architectural protein abundance and pericentromeric satellite expansion.

Damian Dudka, Keagan Beeravolu, Jun Ma, Michael A Lampson.

  Long-read sequencing has enabled precise measurements of highly repetitive centromeric satellites and their rapid divergence between species.1,2,3,4,5,6,7 Large satellite arrays emerge from libraries of shorter arrays via stochastic expansions,8,9 but understanding the selective pressures constraining such expansions remains a major challenge. Here, using the mouse "major" satellite as a model, we reveal reciprocal functional constraints between increasing satellite copy number and abundance of a conserved architectural protein in female meiosis. We show that HMGA2 (high mobility group AT-hook 2) is enriched at major satellite, and its expression correlates with major satellite copy number: both are high in Mus musculus compared to the closely related Mus spretus. To test functional constraints, we modulated HMGA2 abundance by depletion or overexpression and used a musculus/spretus hybrid to generate oocytes with intermediate HMGA2 expression and major satellite copy number. We find that HMGA2 depletion disrupts major satellite packaging in major satellite-rich musculus, but not hybrid, oocytes, indicating that increasing copy number requires high HMGA2 expression. Conversely, HMGA2 overexpression disrupts chromosome segregation in major satellite-poor spretus, but not hybrid, oocytes, indicating that high HMGA2 expression requires expanded major satellite arrays. Based on these results, we propose a co-evolution model in which satellite expansion is constrained by architectural protein abundance, whereas protein abundance is constrained reciprocally by satellite array size.

Keywords:  HMGA2; architectural proteins; centromere; female meiosis; mouse oocytes; satellite DNA; satellite evolution; satellite expansion

DOI:  https://doi.org/10.1016/j.cub.2026.10.039
Nucleic Acids Res. 2026 Nov 10. pii: gkag968. [Epub ahead of print]54(21):

Transcription factor 3 cooperates with CXXC finger protein 1 to regulate histone H3K4 trimethylation and developmental competence in mouse oocytes.

Yue-Xin Qiu, Chi Zhang, Lan-Rui Cao, Bo-Feng Liu, Qi Chen, Wei-Jie Yang, Yuan-Lin He, You-Qiang Su, Han Zhao, Wei Xie, Heng-Yu Fan, Jing Li.

During oogenesis, the establishment of oocyte-specific gene expression relies on epigenetic and transcriptional remodeling. Both histone modifications and transcription factors are crucial for the oocyte to acquire developmental competence; however, the mechanisms involved remain incompletely understood. Here, we identify transcription factor 3 (TCF3), an E-protein family member, as a key maternal regulator of oocyte developmental potential. Oocyte-specific deletion of Tcf3 results in female infertility, characterized by impaired meiotic maturation and early embryonic arrest at the two-cell stage. These defects are associated with defective maternal mRNA clearance and disrupted establishment of the H3K4me3 landscape in maturing oocytes. Mechanistically, we demonstrate that TCF3 directs H3K4me3 deposition at target gene promoters through interaction with CXXC finger protein 1 (CXXC1), the core subunit of the SETD1 histone methyltransferase complex. Importantly, this TCF3-CXXC1 interaction depends on their DNA-binding activity, highlighting the specificity of TCF3 in coordinating with CXXC1 to regulate maternal target genes, such as Pabpn1l. Together, our findings uncover a transcription factor-driven mechanism of epigenetic reprogramming that is essential for the maternal-to-zygotic transition.

DOI: https://doi.org/10.1093/nar/gkag968
J Ovarian Res. 2026 Aug 12. pii: 336. [Epub ahead of print]19(1):

SCAN-seq2 reveals mitochondrial metabolic alterations and proteostasis-related transcriptional signatures during human oocyte aging.

Zheqiao Bai, Canxin Wen, Honghong Jiang, Qihang Wang, Dingchuan Peng, Yicheng Wang, Wendan Zhang, Zhe Zhang, Yiyao Fu, Wei Shang.

   BACKGROUND: Ovarian aging, characterized by declines in both oocyte quantity and quality, represents a major challenge to female reproductive health. However, the age-associated transcriptional alterations underlying human oocyte aging remain incompletely understood.
RESULTS: Differential expression analysis between young and aged oocytes identified 63 age-associated differentially expressed genes, including increased expression of ribosome-associated genes, oxidative-phosphorylation-related genes such as COX5B and UQCRC2, the ubiquitin-associated gene UBA52, and mtDNA-encoded OXPHOS transcripts including MT-ND4 and MT-ND4L, together with reduced expression of the antioxidant-response gene GSTA1 and the mitochondrial respiratory-chain gene NDUFA9. Functional enrichment analyses revealed biological processes related mainly to translation, protein targeting, ribosomal functions, and oxidative phosphorylation. Further subcluster analysis identified an aged-enriched oocyte population with broader mitochondrial-related transcriptional alterations and enrichment of DNA-damage-response pathways. Subsequent PPI analysis of the intersecting genes identified two exploratory functional modules related to mitochondrial respiratory-chain processes and ribosome/ubiquitin-associated proteostasis.
CONCLUSIONS: These findings highlight age-associated transcriptional signatures in human oocytes involving mitochondrial metabolism and proteostasis-associated processes, and reveal molecular heterogeneity among aged oocyte populations. Together, these results provide insights into the molecular changes associated with human oocyte aging and establish a transcriptomic framework for future studies of reproductive aging.

Keywords:  Long-read single-cell RNA sequencing; Mitochondrial metabolism; Oocytes; Ovarian aging; Protein homeostasis; Transcriptional heterogeneity

DOI:  https://doi.org/10.1186/s13048-026-02220-9
Biol Reprod. 2026 Nov 14. pii: ioag250. [Epub ahead of print]

Label-free imaging reveals lipid droplet dynamics during mouse preimplantation development.

Hao Sun, Yanan Qi, Chen Liang, Yichuan Zhang, Tianxia Xiao, Yuxin Luo, Yang Yu.

  Preimplantation embryo development is fundamental to understanding developmental biology and reproductive medicine. Its process requires precise spatiotemporal regulations in which lipid metabolism plays a crucial role. The spatiotemporal dynamics of lipid droplets (LDs), which are important components of embryonic lipid metabolism, in individual embryos remain obscure because of technical limitations. To address this challenge, we developed a submicrometre-level 3D imaging and analysis method based on a label-free imaging system (FI) to quantitatively assess lipid amounts and profiles in individual embryos. Using a third-harmonic generation (THG) channel, LDs were identified and quantified in individual embryos. Our findings revealed that the morphological characteristics of LDs in oocytes vary across different mouse strains. Notably, we also discovered that the estimation of total LD volume dynamically changes during the preimplantation stage. Surprisingly, the accumulation of LDs from the zygote stage to the 4-cell stage is crucial for embryonic development to term. Furthermore, abnormal transcriptomes were observed in 4-cell embryos with LD deficiency. These findings support further investigation of LD characteristics as potential indicators of oocyte and embryo developmental competence. Overall, our results highlight label-free imaging as an available method for studying LDs in embryos and selecting normal embryos. This imaging and analysis system has great potential for animal breeding and clinically assisted reproduction.

Keywords:  developmental potential; embryo development; label-free imaging; lipid droplet

DOI:  https://doi.org/10.1093/biolre/ioag250
bioRxiv. 2026 Oct 16. pii: 2026.10.14.759140. [Epub ahead of print]

Unilateral gene expression via maternally controlled zygotic recombination in Drosophila.

Timothy A Currier, David Tadres, Janina E Troper, Yandan Wang, Thomas R Clandinin.

Structural and functional asymmetries are ubiquitous in bilaterians, but tools for unilateral genetic access have been lacking, a methodological gap that has limited mechanistic dissections of lateralized cellular functions. We developed the Maternally Controlled Zygotic Recombination (MCZR) system to overcome this limitation in Drosophila , co-opting the regulatory machinery of the maternal-to-zygotic transition to enable somatic recombination during early embryonic development. Targeting recombinase activity to this early window generates large somatic mosaics that frequently split across the anatomical midline. In conjunction with cell type-specific driver lines, this approach provides a reliable, scalable, and user-friendly platform for unilateral transgene expression. In proof-of-concept experiments, we apply our tool to the question of locomotor control, illustrating how MCZR can be used to unilaterally manipulate or monitor a cell type of interest. Overall, the MCZR system unlocks previously inaccessible experimental avenues across neuroscience, cell biology, and developmental biology.

DOI: https://doi.org/10.64898/2026.10.14.759140