During meiosis, telomere clustering and motion promote the pairing between homologous chromosomes. In budding yeast, actin filaments in the cytoplasm drive the motion of a Linker Nucleoskeleton and Cytoskeleton (LINC) complex with the SUN-domain protein, Mps3, which tethers and moves telomeres to the nuclear envelope (NE). In this study, we analyzed the roles of two actin-binding proteins, essential Type-V myosin (Myo2) and Sac6 fimbrin, which bundles actin filaments in cables, in meiotic Mps3 motion on the NE. Meiosis-specific depletion of MYO2 reduced the motion of Mps3 patches without affecting cytoplasmic actin cables during meiotic prophase I, confirming actin/myosin-dependent Mps3 motion. Moreover, Myo2 plays a critical role in the maintenance of Mps3 clustering and, probably, telomere clustering in the absence of Rec8, a component of the meiotic cohesin. The deletion of SAC6, which is critical for force generation in the cytoplasm, during meiosis largely reduced cytoplasmic actin cables without affecting Mps3 localization and motion. Likely, Sac6-mediated actin filament bundling is not critical for the meiotic motion of Mps3 patches. Our study suggests that actin polymerization and Myo2-mediated force are involved in the meiotic motion of the yeast LINC complex.

The translocase of the outer mitochondrial membrane (TOM) complex is the entry gate for mitochondrial proteins synthesized in the cytosol. Previous biochemical studies indicated that the TOM complex functions as a trimer and exists in a dynamic equilibrium with a Tom22-lacking dimer in intact mitochondria. In contrast, recent cryo-electron microscopy (cryo-EM) studies revealed near-atomic structures of the Tom22-containing core dimer. However, the relationship between the core dimer and the functional trimer remains unclear. Here, we analyzed the oligomeric organization and structural properties of purified yeast TOM complexes using high-speed atomic force microscopy (HS-AFM). Purified yeast TOM complexes predominantly adopted a trimeric organization but underwent deformation and dissociation during repeated HS-AFM scanning, leaving dimeric and monomeric particles. Trimeric particles exhibited spherical shapes consistent with previous crosslinking models, whereas dissociated dimers closely resembled TOM core-dimer structures determined by cryo-EM. HS-AFM also revealed the peripheral localization of the Tom20 receptor and enabled direct visualization of substrate-TOM interactions, with TOM association accompanied by reduced substrate mobility. Together, these findings provide quantitative and structural evidence for a predominantly trimeric organization of the purified TOM complex and suggest that the trimer contains a stable core-dimer unit with a more loosely associated third Tom40-containing unit.

Mechanical cues influence cell behavior and fate and are frequently accompanied by changes in nuclear shape; however, how epithelial nuclei accommodate such deformations remains incompletely understood. In this article, we investigated the formation and regulation of nuclear wrinkles (NWs), inward folds of the nuclear envelope, in human epithelial cells. Using quantitative confocal imaging in 2.5D spheroid cultures and controlled 2D monolayers, we found that NWs formed frequently in MCF10A cells but rarely in hTERT-RPE1 cells, indicating pronounced cell-type specificity. NW frequency increased with cell density and was tightly associated with coordinated geometric changes consistent with nuclear rounding. Disruption of F-actin organization, but not microtubules, robustly induced NW formation, and acute cell rounding triggered by trypsinization was sufficient to induce widespread wrinkling across multiple cell types. Live-cell imaging revealed that NWs are dynamic and reversible at low cell density but become stabilized under sustained confinement. NW formation occurred without detectable nuclear envelope rupture, DNA damage, or stress-associated histone phosphorylation. Quantitative analysis supports a passive geometric model in which redistribution of excess nuclear surface area accommodates nuclear shape remodeling, allowing epithelial nuclei to buffer mechanical constraints while preserving nuclear integrity.

Real-time visualization of specific mRNA expression in living cells is essential for understanding diverse biological processes; however, many existing approaches require modifications to target genes. In this study, we developed a programmable RNA-mediated bimolecular fluorescence complementation (RmBiFC) system by fusing split Venus fluorescent protein fragments with the Pumilio homology domain as a modular RNA-binding domain. Using murine leukemia virus mRNA as a model target, we systematically optimized the orientation of the probes and demonstrated robust detection of cells expressing target mRNA. This system enables live-cell imaging of target mRNA-expressing cells without modifying the target gene. This provides a valuable means of tracking cells expressing wild-type genes, which is challenging to achieve using conventional reporter-based approaches. The RmBiFC system represents a versatile and non-invasive platform with broad potential for identifying specific cell populations based on their transcriptomic profiles at the cellular level.

The liver maintains tissue homeostasis both by undergoing regeneration and by eliminating abnormal or injured hepatocytes. The transcriptional coactivator YAP in collaboration with the TEAD family of transcription factors regulates hepatocyte proliferation. It has also been associated with injured hepatocyte elimination whereby YAP-active injured hepatocytes are extruded into the sinusoidal lumen and undergo cell death followed by macrophage phagocytosis. However, the molecular mechanisms underlying this process are unknown. To address this, we performed RNA-seq analysis in YAP-active injured hepatocytes that are eliminated from the liver. We found increased expression of multiple genes associated with cell cycle arrest and cytoskeletal remodeling. Ligand-receptor analysis using single-cell spatial transcriptomics showed that YAP-active hepatocytes express the secreted factors CSF1 and CCL2, which promote macrophage recruitment and activation. ATAC-seq analysis in YAP-active hepatocytes revealed a significant increase in chromatin accessibility at regions containing CTCF-binding motifs, and the YAP-TEAD4 complex associated with CTCF in the nucleus. These results indicate that a YAP-TEAD-CTCF axis shapes the gene expression program underlying injured hepatocyte elimination through chromatin structural remodeling, resulting in liver homeostasis.

Pulmonary fibrosis is a progressive and life-threatening lung disorder characterized by excessive fibrogenesis and impaired respiratory function. Nerandomilast, a preferential phosphodiesterase 4B inhibitor, is currently approved for the treatment of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis in several countries following its demonstrated clinical efficacy in Phase III trials. However, its cellular mechanisms of action remain incompletely understood. In this study, we investigated the effects of nerandomilast on a bleomycin-induced mouse model of lung fibrosis. Nerandomilast treatment attenuates fibrotic remodeling and preserves alveolar epithelial architecture. Single-cell transcriptomic analyses revealed altered alveolar epithelial cell state dynamics accompanied by increased cell cycle-associated pathways in alveolar type 2 cells and an increased relative abundance of alveolar type 2 cells. Consistent with the single-cell findings, nerandomilast was associated with an increased SFTPC-positive area and the preservation of alveolar epithelial architecture in vivo. Collectively, our findings suggest that nerandomilast attenuates fibrotic remodeling while modulating alveolar epithelial cell state dynamics, which may provide a possible cellular explanation for its clinical efficacy in patients with pulmonary fibrosis.

Statins, inhibitors of HMG-CoA reductase, exert immunomodulatory effects beyond lipid lowering, yet how they regulate T helper (Th) cell differentiation remains poorly understood. We show that fluvastatin administration to C57BL/6 mice for 7 days suppressed interferon-γ and elevated interleukin-4 production by splenic CD4[+] T cells, shifting the immune balance toward Th2 without altering splenocyte numbers or major immune cell subset proportions. This effect was not shared by rosuvastatin, suggesting that lipophilicity-dependent cellular uptake influences immunomodulatory potency. In vitro experiments confirmed a direct Th2-promoting action of fluvastatin on CD4[+] T cells. Basophils were excluded as mediating cells, as fluvastatin suppressed rather than enhanced basophil interleukin-4 production. Continuous fluvastatin exposure during granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven dendritic cell (DC) differentiation altered the phenotype of the resulting DCs and markedly enhanced their Th2-polarizing capacity in co-cultures with antigen-specific CD4[+] T cells. These functional changes were accompanied by alterations in DC surface molecule expression, although their causal contribution remains to be established. These findings indicate that continuous fluvastatin exposure during DC differentiation is associated with an altered DC phenotype and enhanced Th2-polarizing capacity.

Epithelial-mesenchymal transition (EMT) is crucial for initiation of cancer metastasis. EMT-induced epithelial cancer cells gain stemness characteristics, which enhance cancer malignancy and chemoresistance. Therefore, it is important to clarify the function of EMT-related genes for development of therapeutics for cancer metastasis. Here, we showed that Signal-transducing adaptor protein-2 (STAP-2) inhibits EMT in cancer cells through repressing SMAD-mediated ZEB1 expression, which is a master transcription factor of EMT. STAP-2 inhibits the interaction between SMAD3 and SMAD4, resulting in the downregulation of SMAD2/3/4 complex formation and TGF-β signal-induced gene expression. STAP-2 expression was repressed by SMAD2/3-mediated TGF-β signals and activated by OVOL1, which is one of the EMT repressor transcription factors. Our study showed that STAP-2 is a novel EMT repressor gene which represses ZEB1 expression and motility of cancer cells.

Advances in long-read sequencing and Hi-C scaffolding have made chromosome-level genome assembly increasingly accessible to individual laboratories, shifting genome research from large consortium-led projects toward investigator-driven studies across diverse taxa. This transition allows researchers to select organisms based on biological questions rather than the prior availability of genomic resources. In this review, we summarize the core experimental and computational steps for generating, evaluating, and annotating chromosome-level assemblies, and examine how they have advanced research in non-model organisms and genetically complex systems. Representative case studies illustrate four major contributions: resolving structural variation and lineage-specific genome architecture, linking genome organization to phenotypic innovation and plasticity, reconstructing deep chromosome evolution and macrosynteny, and distinguishing homologous and homoeologous chromosomes in polyploid genomes. These examples show that chromosome-level assemblies provide more than complete reference sequences. They establish a continuous genomic coordinate system through which genes, regulatory elements, transposable element insertions, sequence variants, and cellular states can be interpreted within broader chromosomal, population, and evolutionary contexts. We describe this integrative perspective as "glocal biology." Future progress will require pangenomic, population-scale, and haplotype-resolved resources integrated with multi-omics and functional analyses. Collectively, chromosome-level genomics is reshaping life science by embedding molecular functions within chromosomal and evolutionary contexts.

Small-scale recurring international workshops dedicated to the cell cycle have become well established in Europe and the United States, but not in Japan. To establish such a workshop in Japan, four principal investigators at the Okinawa Institute of Science and Technology Graduate University (OIST) organized the First International Workshop on Cell Division Cycles, entitled "Emerging Concepts in Cell Division Cycles 2026-From Early Development to Cancer and Aging," in Okinawa, Japan, from March 2 to 5, 2026. The meeting brought together 17 world-leading experts and a total of 74 participants from diverse fields spanning cell division, cancer, and aging. The speakers presented cutting-edge studies employing a wide range of advanced approaches, including large-scale translational isoform analyses, new experimental systems and model organisms, ultrastructure expansion microscopy, and anti-aging strategies. These advances highlighted recent progress in understanding the mechanisms that ensure faithful genome inheritance and their relevance to development, disease, and evolution. Here, we summarize the 36 oral presentations, together with photographs from the workshop, and share our reflections and perspectives with the community in the hope that the OIST Cell Division Workshop will continue to grow as a recurring international forum for cell division and cell cycle research.

Using a genetic screening approach based on an inducible gene-activating system and cell sorting, Down syndrome critical region 3 (DSCR3) was isolated as a gene whose overexpression increased cell size. Fibroblasts derived from individuals with Down syndrome (DS) exhibit elevated DSCR3 expression at both the mRNA and protein levels, correlating with increased cell volume compared to fibroblasts from healthy donors. Despite a slower proliferation rate, DS fibroblasts demonstrate higher basal and maximal mitochondrial respiration, suggesting enhanced metabolic activity associated with increased cell size. siRNA-mediated knockdown of DSCR3 reduces cell size in both DS and normal fibroblasts, indicating its general role in cell size regulation. As DSCR3 is a component of the retriever complex involved in endosomal cargo recycling, these findings position membrane protein trafficking as a novel module for cell size control.

Jasmonate-mediated defense responses redirect plant resources from growth to defense, imposing significant demands on the nitrogen economy to produce nitrogenous compounds, such as alkaloids. However, the mechanisms by which plants maintain essential central metabolic processes, such as nucleotide synthesis, under nitrogen resource competition remain unclear. Therefore, in this study, we characterized the nucleobase cation symporter NtNCS1 in Nicotiana tabacum. Notably, NtNCS1 mRNA exhibited opposing organ-specific regulation by jasmonic acid, with induction in roots (the site of nicotine synthesis) but repression in leaves. NtNCS1 was localized to the plastid envelope in metabolically active cells, including mesophyll, phloem-associated, and, notably, guard cells. This dual regulation suggests that NtNCS1 plays a key role in reallocating nitrogen resources. In roots, its expression possibly contributes to maintaining the essential nucleotide pools for basal metabolism when nitrogen is diverted to alkaloid production. Conversely, its repression in leaves possibly conserves nitrogen by downregulating growth, thereby reallocating resources to defense. Overall, this study highlights the potential roles of NCS1 transporters in safeguarding central metabolism and mediating the plant growth-defense trade-off.

Human norovirus (HuNoV) is a major cause of acute viral gastroenteritis. Although it can be replicated in vitro using human intestinal enteroids (HIEs), generating high-titer viral laboratory stocks remains challenging due to low infection and passage efficiencies. Interferon response and chemokine signaling may be key host pathways that restrict efficient HuNoV replication. Here, we evaluated the effect of their inhibitors, ruxolitinib-a Janus kinase (JAK) 1/JAK2 inhibitor-and TAK-779-a C-X-C motif chemokine receptor 3 (CXCR3)/C-C motif chemokine receptor (CCR) 5/CCR2 antagonist-on HuNoV replication in wild-type jejunal HIEs. TAK-779 increased GII.17 HuNoV replication by 2.3- and 6.0-fold at 48 and 96 h postinfection (hpi), respectively, compared with the DMSO-treated control. In contrast, ruxolitinib alone did not affect viral replication. Notably, simultaneous treatment with these compounds further enhanced GII.17 replication by 6.0- and 10.7-fold at 48 and 96 hpi, respectively, which enabled serial passaging. These findings imply that the simultaneous suppression of these pathways potentially benefits GII.17 HuNoV replication.