Genes to Cells最新文献

The VIIth International Workshop on SOX Transcription Factors (SOX2025) was held at the Karuizawa Prince Hotel West, Nagano, Japan, from September 8 to 11, 2025. The meeting marked the 20th anniversary of the SOX conference series and brought together 83 participants from 17 countries. Researchers presented cutting-edge studies spanning structural biology, stem cell regulation, neurodevelopment, sex determination, germ cell biology, vascular development and disease mechanisms including oncology, genetic disorders and acquired diseases. Educational and special lectures provided both historical perspectives and forward-looking visions, framing the scientific discussions in the context of developmental biology and medical science. With a rich program of oral presentations, posters, and discussions, SOX2025 strengthened the global community of SOX researchers and underscored the broad significance of these transcription factors in biology and disease.

Histone H3 lysine 9 (H3K9) methylation and heterochromatin protein 1 (HP1) are well-conserved heterochromatin epigenomes and their reader molecules. However, the details of the importance of them in heterochromatin formation still remain unclear. One reason for this is system redundancy, as multiple HP1 family proteins exist, as well as HP1 itself serving as hubs for various effector factors. To overcome these issues, we took a synthetic biology approach and introduced H3K9 methylation catalyzed by mouse H3K9 methyltransferases and HP1s into budding yeast, Saccharomyces cerevisiae (S. cerevisiae) which doesn't have this system, and examined its impact on transcription and chromatin compaction. We observed that the mammalian H3K9 methyltransferase can induce genome-wide H3K9 di- and tri-methylation in the S. cerevisiae, mainly in the gene body region, and HP1 accumulates over the H3K9 methylated regions. The forced expression of H3K9 methyltransferase and HP1 had little impact on transcription. Furthermore, Hi-C-seq analysis revealed no significant effects on the chromatin 3D structure. These results suggest that although H3K9 methylation and the recruitment of HP1 play essential roles in the epigenetic regulation of heterochromatin, they alone are not sufficient to alter the higher-order chromatin structure, at least in the gene body regions in S. cerevisiae.

Classic cadherin cell–cell adhesion molecules with self-organizing activities play roles in segregating distinct populations of cells at developing brain regions and/or boundaries. However, the protein dynamics of each cadherin subclass in the mouse embryonic brain is poorly described due to the low antigenicity. Here, we generate Cdh6-HA and Cdh8-PA tag knock-in (KI) mice by CRISPR/Cas9-mediated genome editing and establish Cdh6^HA/HA; Cdh8^PA/PA; Cdh11^EGFP/EGFP triple tag KI homo mice with normal viability and fertility. Immunostaining with specific antibodies for these tags reveals differential protein expression profiles almost comparable with mRNA in situ hybridization (ISH) results during embryonic brain development. We can additionally detect considerable levels of immunostaining signals outside the mRNA ISH-positive areas, specifically along the nerve tracts, suggesting physiological accumulation of these type II cadherin proteins along axons. By using super-resolution imaging, we further evaluate cadherin subcellular localization dynamics around the zona limitans intrathalamica to confirm that the prosomere 2/3 compartment boundary at E12.5 is maintained by the distinctive integration of Cdh6 or Cdh11 at apical attachment sites of the ventricular cells. These results highlight the value of the genetic tag KI strategy for proteins with low antigenicity and the functional relevance of type II classic cadherins in brain development.

Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatohepatitis (MASH) frequently coexist and are mechanistically linked via insulin resistance, lipotoxicity, and chronic inflammation. Cholic acid (CA), a primary bile acid (BA), modulates metabolic and immune pathways by influencing BA composition and the gut microbiota. In this study, we examined the role of dietary CA in the modulation of T2DM and MASH in Tsumura Suzuki obese diabetes (TSOD) mice, a model of spontaneous obesity and diabetes. Mice were fed a high-fat, high-cholesterol diet with or without CA (iHFC and CA(−) iHFC diets, respectively). CA supplementation significantly improved hyperglycemia and hyperinsulinemia, independent of adipose tissue inflammation. These metabolic benefits were associated with an increased intestinal abundance of Akkermansia muciniphila and elevated ileal expression of fibroblast growth factor 15 (FGF-15), suggesting activation of the FXR–FGF-15 axis. However, CA also exacerbated MASH, accompanied by increased hepatic inflammation, fibrosis, and accumulation of hepatotoxic BAs, including deoxycholic acid and taurodeoxycholic acid. The removal of CA mitigated these hepatic changes while abolishing glycemic improvement. Accordingly, CA can exert opposing effects in TSOD mice—ameliorating T2DM while worsening MASH—highlighting the need for caution when targeting BA pathways in metabolic diseases.

Cellular senescence is caused by various stresses, including DNA damage, oxidative stress, oncogene activation, and telomere shortening. However, the detailed molecular mechanisms of cellular senescence have yet to be elucidated. Recently, using comparative transcriptomics and quantitative PCR, we identified several genes that are specifically upregulated in senescent cells in a p53-dependent manner, including Epsin 3 (EPN3). However, the functional relevance of EPN3 to senescence has not yet been defined. Here, we performed functional analyses to investigate the relationship between EPN3 and the senescence program. We found that EPN3 knockdown suppressed senescent phenotypes induced by DNA damage. Furthermore, ectopic expression of EPN3 induced senescence accompanied by increased reactive oxygen species (ROS) and accumulation of DNA damage. Furthermore, EPN3-induced DNA damage was suppressed by genetic and pharmacological inhibition of Rac1. Finally, treatment with ROS scavengers, N-acetyl-l-cysteine (NAC) and l-Ascorbic Acid (LAA), prevented EPN3-induced DNA damage, and a Rac1 inhibitor reduced ROS levels in EPN3-expressing stable clones. These results indicate that EPN3 induces DNA damage and promotes senescence via Rac1 activity and ROS generation.