International Journal of Molecular Sciences最新文献

{"title":"Heart Failure Biomarkers-Pathophysiology, Diagnosis, Prognosis and Clinical Relevance.","authors":"Bianca-Ștefania Profire, Florentina Geanina Lupașcu, Cristian Stătescu, Victorița Șorodoc, Radu-Andy Sascău, Lenuța Profire, Laurențiu Șorodoc","doi":"10.3390/ijms26199740","DOIUrl":"10.3390/ijms26199740","url":null,"abstract":"<p><p>Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and maladaptive neurohormonal activation, representing one of the leading causes of morbidity, hospitalization, and mortality worldwide. Both its incidence and prevalence continue to rise, largely as a consequence of population aging and the increasing burden of cardiovascular risk factors. The pathogenesis of HF is multifactorial, involving a dynamic interplay between inflammation and neurohormonal activation, ultimately leading to cardiac remodeling, diastolic dysfunction, and impaired cardiac output. In this context, numerous biomarkers have been investigated for diagnosis and prognosis utility in patients with HF. According to their underlying pathophysiological mechanisms, biomarkers in HF can be broadly categorized as indicators of inflammation, oxidative stress, cardiac remodeling, myocardial stress, neurohormonal activation, and cardiomyocyte injury. This review summarizes current knowledge on the pathophysiological basis of HF and highlights the diagnostic and prognostic relevance of circulating biomarkers, emphasizing their role in linking disease mechanisms with clinical management.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of Fasting Endogenous Erythritol and Erythronate Concentrations in Humans: Cross-Sectional and Post-Bariatric Surgery Analyses.","authors":"Emilie Flad, Anita Altstädt, Jürgen Drewe, Stefan Gaugler, Christoph Beglinger, Ralph Peterli, Bettina K Wölnerhanssen, Anne Christin Meyer-Gerspach","doi":"10.3390/ijms26199763","DOIUrl":"10.3390/ijms26199763","url":null,"abstract":"<p><p>The sugar alcohol erythritol occurs naturally in fruits and fermented foods, is used as a sweetener, and is also endogenously synthesized via the pentose-phosphate pathway and metabolized into erythronate. Untargeted metabolomic studies have associated elevated plasma erythritol and erythronate concentrations with metabolic disorders, while weight loss has been linked to decreased plasma erythritol concentrations. In this trial, two complementary analyses were performed to identify predictors of fasting erythritol and erythronate concentrations across different populations and to assess changes in these metabolites following bariatric surgery-induced weight loss. Fasting plasma samples from 30 lean adolescents, 50 lean adults, and 138 adults with obesity (including 15 who had undergone bariatric surgery) were analyzed to measure erythritol, erythronate, glucose, and insulin concentrations. Across all populations, age but not body mass index (BMI), glucose, or insulin, was a significant predictor of fasting erythritol concentrations. Fasting erythronate concentrations were associated with both age and BMI. Post-surgery, change in BMI but not fasting glucose or insulin was a predictor of changes in fasting erythritol concentrations, while time was the only predictor of changes in fasting erythronate concentrations. Although the metabolic processes regulating the endogenous erythritol and erythronate production remain unclear, our findings suggest that age-related physiological changes may influence fasting concentrations of both erythritol and erythronate.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Duality of Collagens in Metastases of Solid Tumors.","authors":"Michelle Carnazza, Danielle Quaranto, Nicole DeSouza, Xiu-Min Li, Raj K Tiwari, Julie S Di Martino, Jan Geliebter","doi":"10.3390/ijms26199745","DOIUrl":"10.3390/ijms26199745","url":null,"abstract":"<p><p>Metastases are responsible for the majority of cancer-related deaths and remain one of the most complex and therapeutically challenging hallmarks of cancer. The metastatic cascade involves a multistep process by which cancer cells invade local tissue, enter and survive in circulation, extravasate, and ultimately colonize distant organs. Increasingly, the tumor microenvironment (TME), particularly the extracellular matrix (ECM), has emerged as a central regulator of these steps. Far from being a passive scaffold, the ECM actively influences cancer progression through its biochemical signals, structural properties, and dynamic remodeling. Among ECM components, collagens play a particularly pivotal role by mediating tumor cell adhesion, migration, invasion, survival, immune evasion, and therapeutic resistance. This narrative review synthesizes current knowledge of the dual roles of collagen in the metastatic process, with a focus on the cellular and molecular mechanisms. We highlight how altered ECM architecture and signaling contribute to metastatic niche formation and explore the potential of targeting ECM components as a strategy to enhance cancer therapy and improve patient outcomes.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Establishment of a Sheep Embryo Genomic Selection System.","authors":"Yubing Wang, Hao Qin, Ke Li, Jia Hao, Xingyuan Liu, Dayong Chen, Lei Cheng, Huijie He, Riga Wu, Yingjie Wu, Yinjuan Wang, Min Guo, Qin Li, Lei An, Jianhui Tian, Hongbing Han, Guangyin Xi","doi":"10.3390/ijms26199738","DOIUrl":"10.3390/ijms26199738","url":null,"abstract":"<p><p>Embryo genomic selection (EGS) is a contemporary breeding strategy that combines genomic selection (GS) methodology with embryo biotechnology. By conducting genotyping and genomic prediction at the pre-implantation stage, embryos with superior breeding value can be identified for transfer, markedly increasing breeding efficiency while reducing the uncertainty and temporal expenditure associated with conventional GS. This study establishes a reliable embryo biopsy-based GS pipeline for sheep, incorporating optimized whole-genome amplification and microcell genotyping techniques. We developed a high-efficiency in vitro sheep embryo production platform compatible with embryo biopsy. Systematic comparison of Multiple Displacement Amplification (MDA) and Multiple Annealing and Looping Based Amplification Cycles (MALBAC) whole-genome amplification systems yielded high-quality genotypes from biopsy samples of embryos containing as few as 10 cells. Imputation using 10× whole-genome sequencing data significantly increased both genotype call rates and accuracy. High concordance was observed between embryo and lamb genotypes, and genomic estimated breeding values (GEBVs) for key growth traits exhibited strong correlations (R²: 0.91-0.98). This system enables accurate preimplantation genomic evaluation and provides an efficient strategy to accelerate genetic improvement in sheep breeding programs.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic-Driven Drug Repurposing Reveals SP600125 as a Promising Drug Candidate for the Treatment of Glial-Mesenchymal Transition in Glioblastoma.","authors":"Kirill V Odarenko, Marina A Zenkova, Andrey V Markov","doi":"10.3390/ijms26199772","DOIUrl":"10.3390/ijms26199772","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is an aggressive brain cancer characterized by highly invasive growth driven by glial-mesenchymal transition (GMT). Given the urgent need for effective therapies targeting this process, we aimed to discover potential GMT inhibitors using transcriptomic-based repurposing applied to both approved and experimental drugs. Deep bioinformatic analysis of transcriptomic data from GBM patient tumors and GBM cell lines with mesenchymal phenotype using gene set variation analysis (GSVA), weighted gene co-expression network analysis (WGCNA), reconstruction of GMT-related gene association networks, gene set enrichment analysis (GSEA), and the search for correlation with transcriptomic profiles of known GMT markers, revealed a novel 31-gene GMT signature applicable as relevant input data for the connectivity map-based drug repurposing study. Using this gene signature, a number of small-molecule compounds were predicted as potent anti-GMT agents. Further ranking according to their blood-brain barrier permeability, as well as structural and transcriptomic similarities to known anti-GBM drugs, revealed SP600125, vemurafenib, FG-7142, dibenzoylmethane, and phensuximide as the most promising for GMT inhibition. In vitro validation showed that SP600125, which is most closely associated with GMT-related hub genes, effectively inhibited TGF-β1- and chemical hypoxia-induced GMT in U87 GBM cells by reducing morphological changes, migration, vasculogenic mimicry, and mesenchymal marker expression. These results clearly demonstrate the applicability of connectivity mapping as a powerful tool to accelerate the discovery of effective GMT-targeting therapies for GBM and significantly expand our understanding of the antitumor potential of SP600125.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Search of Molecular Correlates of Fibromyalgia: The Quest for Objective Diagnosis and Effective Treatments.","authors":"Sveva Bonomi, Elisa Oltra, Tiziana Alberio","doi":"10.3390/ijms26199762","DOIUrl":"10.3390/ijms26199762","url":null,"abstract":"<p><p>Fibromyalgia is a chronic syndrome characterized by widespread musculoskeletal pain, fatigue, non-restorative sleep, and cognitive impairment. Its pathogenesis reflects a complex interplay between central and peripheral mechanisms, including altered pain modulation, neuroinflammation, mitochondrial dysfunction, autonomic imbalance, and genetic and epigenetic factors. Evidence from neuroimaging, omics studies, and neurophysiology supports this multifactorial model. Epidemiological updates confirm a global prevalence of 2-8%, with a strong female predominance and a significant impact on quality of life and healthcare costs. Diagnostic criteria have evolved from the 1990 American College of Rheumatology tender points to the 2010/2011 revisions and the 2016 update, improving case ascertainment but still lacking objective biomarkers. Recent omics and systems biology approaches have revealed transcriptional, proteomic, and metabolic signatures that may enable molecularly informed stratification. Therapeutic management remains multidisciplinary, combining pharmacological interventions (e.g., duloxetine, pregabalin, milnacipran) with non-pharmacological strategies such as graded aerobic exercise and cognitive behavioral therapy. Emerging approaches include drug repurposing to target neuroinflammation, mitochondrial dysfunction, and nociceptive pathways. Despite promising advances, progress is limited by small sample sizes, heterogeneous cohorts, and lack of standardization across studies. Future priorities include large-scale validation of biomarkers, integration of multi-omics with clinical phenotyping, and the design of precision-guided trials. By synthesizing mechanistic insights with clinical evidence, this review provides an updated framework for the diagnosis and management of fibromyalgia, highlighting pathways toward biomarker-guided, personalized medicine.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering CO₂-Fixing Carboxysome into <i>Saccharomyces cerevisiae</i> to Improve Ethanol Production.","authors":"Mengqi Li, Simin Zeng, Yunling Guo, Jie Ji, Qiuling Fan, Deqiang Duanmu","doi":"10.3390/ijms26199759","DOIUrl":"10.3390/ijms26199759","url":null,"abstract":"<p><p>Bacterial microcompartments (BMCs) are intracellular structures for compartmentalizing specific metabolic pathways in bacteria. As a unique type of BMCs, carboxysomes utilize protein shells to sequester ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic anhydrase for efficient carbon dioxide (CO₂) fixation. This study aims to reconstruct an α-carboxysome in <i>Saccharomyces cerevisiae</i> and investigate its metabolic effects. Here, genes of the <i>cso</i> operon from <i>Halothiobacillus neapolitanus</i>, Calvin cycle-related enzyme phosphoribulokinase (PRK) from <i>Spinacia oleracea</i>, and two <i>S. cerevisiae</i> chaperone genes, <i>HSP60</i> and <i>HSP10</i>, were introduced into <i>S. cerevisiae</i>. The engineered yeast strain demonstrated assembled and enzymatically active Rubisco, significant increase in ethanol production and reduction in the byproduct glycerol. Formation of the α-carboxysome structures was observed after purification by sucrose density gradient centrifugation. The engineered yeast strain harboring functional α-carboxysome has the potential for enhancing bioethanol production.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genes Associated with Apoptosis in an Experimental Breast Cancer Model.","authors":"Gloria M Calaf, Leodan A Crispin","doi":"10.3390/ijms26199735","DOIUrl":"10.3390/ijms26199735","url":null,"abstract":"<p><p>Breast cancer remains a leading cause of global mortality. According to international cancer data, significant progress has been made in treating breast cancer; however, metastasis and drug resistance continue to be the primary causes of mortality for many patients. This study investigated the modulation of apoptosis-related genes in response to ionizing radiation and estrogen exposure based on a human breast epithelial cell model (MCF-10F and its transformed variants: Estrogen, Alpha3, Alpha5, Tumor2) previously established, where cells were treated with high linear energy transfer alpha particles, with or without 17β-estradiol. Gene expression profiling was performed using an Affymetrix U133A microarray, and bioinformatic analyses assessed differential expression, estrogen receptor status, and correlations with overall survival. Distinct gene expression patterns emerged across cell lines and tumor subtypes. <i>TP53</i> expression correlated positively with <i>TP63</i>, <i>BIK</i>, <i>CFLAR</i>, <i>BIRC3</i>, and <i>BCLAF1</i>. <i>TP63</i>, <i>PERP</i>, <i>CFLAR</i>, <i>BCLAF1</i>, <i>GULP1</i>, and <i>BIRC3</i> were elevated in normal tissue, whereas <i>BIK</i>, <i>PHLDA2</i>, and <i>BBC3</i> were upregulated in tumors. ER-positive tumors exhibited higher <i>TP63</i>, <i>BIK</i>, <i>BCLAF1</i>, and <i>BBC3</i> expression, while ER-negative tumors showed increased <i>PERP</i>, <i>CFLAR</i>, <i>BIRC3</i>, and <i>PHLDA2</i>. Notably, elevated <i>BCLAF1</i> expression was associated with poorer survival in Luminal A patients, and high <i>PHLDA2</i> expression correlated with reduced survival in Luminal B cases. These findings indicate that resistance to apoptosis is a fundamental mechanism in breast cancer progression and therapeutic evasion. Breast tumors selectively alter the expression of key genes to promote growth, evade apoptosis, and develop therapeutic resistance. The differential expression and correlations of these apoptosis-related genes highlight their potential as molecular targets for future personalized cancer therapies and as valuable biomarkers for prognostic stratification and predicting therapeutic response.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Interactome Mapping of Human Tau in Drosophila Reveals Progressive Mitochondrial Engagement and Porin/VDAC1-Dependent Modulation of Toxicity.","authors":"Eleni Tsakiri, Martina Samiotaki, Efthimios M C Skoulakis, Katerina Papanikolopoulou","doi":"10.3390/ijms26199741","DOIUrl":"10.3390/ijms26199741","url":null,"abstract":"<p><p>Tau protein misfolding and aggregation are central to Tauopathies, yet the temporal dynamics of Tau interactions in vivo remain poorly understood. Here, we applied quantitative proteomics to demonstrate that the interactome of human Tau in adult Drosophila brains changes dynamically over a 12-day time course, revealing a progressive shift from early cytosolic and ribosomal associations to late enrichment of mitochondrial and synaptic partners. Notably, the mitochondrial pore protein Porin/VDAC1 was identified as a late-stage interactor and functional analyses demonstrated that Tau overexpression impairs mitochondrial respiration, elevates oxidative damage, and disrupts carbohydrate homeostasis. To validate this temporally specific interaction, Porin was downregulated, resulting in reduced Tau mitochondrial association, phosphorylation and aggregation. Paradoxically, however, Porin attenuation exacerbated Tau-induced toxicity, including shortened lifespan, locomotor deficits, and impaired learning. These findings indicate that while Porin facilitates pathological Tau modifications, it is also essential for neuronal resilience, highlighting a complex role in modulating Tau toxicity. Our study provides a temporal map of Tau-associated proteome changes in vivo and identifies mitochondria as critical mediators of Tau-driven neurodegeneration.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ezh2 Loss-of-Function Alters Zebrafish Cerebellum Development.","authors":"Mariette Hanot, Pamela Völkel, Xuefen Le Bourhis, Chann Lagadec, Pierre-Olivier Angrand","doi":"10.3390/ijms26199736","DOIUrl":"10.3390/ijms26199736","url":null,"abstract":"<p><p>EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), plays a critical role in neural development by regulating gene expression through the trimethylation of lysine 27 on histone H3 (H3K27me3), which promotes chromatin remodeling and transcriptional repression. Although PRC2 is known to regulate cell fate specification and gliogenesis, its in vivo functions during vertebrate neurodevelopment, particularly at the level of neuronal subtype differentiation, remain incompletely understood. Here, we investigated the consequences of <i>ezh2</i> loss-of-function during zebrafish brain development, focusing on oligodendrocyte differentiation, cerebellar neurogenesis, and the formation of neurotransmitter-specific neuronal populations. Using whole-mount in situ hybridization, we found that <i>ezh2</i> inactivation does not alter the expression of oligodendrocyte lineage markers, indicating that early oligodendrocyte precursor cell specification and myelination are preserved. However, a significant reduction in cerebellar proliferation was observed in <i>ezh2</i>-deficient larvae, as evidenced by the downregulation of <i>pcna</i> and <i>cyclin A2</i>, while other brain regions remained unaffected. Notably, the expression of <i>atoh1c</i>, a key marker of glutamatergic cerebellar progenitors, was strongly reduced at 5 days post fertilization, suggesting a selective role for <i>ezh2</i> in maintaining cerebellar progenitor identity. This was associated with impaired differentiation of both glutamatergic granule cells and GABAergic Purkinje cells in specific cerebellar subregions. In contrast, the expression of markers for other major neurotransmitter systems remained unaffected, indicating a region-specific requirement for <i>ezh2</i> in neuronal development. Finally, behavioral analysis revealed a hyperlocomotor phenotype in <i>ezh2</i>^-/- larvae, consistent with cerebellar dysfunction. Together, these findings identify <i>ezh2</i> as a key regulator of progenitor maintenance and neuronal differentiation in the cerebellum, highlighting its crucial role in establishing functional cerebellar circuits.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}