'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Sat, 14 Jun 2025 06:12:53 EDT Sat, 14 Jun 2025 06:12:53 EDT jirtle@radonc.duke.edu james001@jirtle.com In vitro processes alter the embryonic disc epigenome and transcriptome in the pre-implantation elongated bovine embryo†. Behrens T, Balasubramanian J, Ivask M, Nõmm M, Kavak A, Secher JB, Kadarmideen HN, Rabaglino MB
Biol Reprod (Jun 2025)

The objective was to quantify the effect of the in vitro procedures on the epigenome and transcriptome of the embryonic disc (ED) and extra-embryonic membranes (EEM) of day 15 in vitro produced (IVP) conceptuses compared to in vivo (IVV) counterparts. IVP embryos (n = 7) were cultured serum-free until transfer at day 7. IVV embryos (n = 9) were conceived by artificial insemination. Animals were flushed at day 15 of gestation, and sections of ED and EEM were subjected to DNA and mRNA extraction for whole genome bisulfite or RNA sequencing. Raw fastq files were aligned to the ARS-UCD1.3 bovine genome. Processed data were integrated through a multi-omics approach based on machine learning to determine the key ontological terms characterizing each embryonic tissue lineage according to their methylome and transcriptome, followed by overrepresentation analyses (adjusted p-value<0.05) of differentially methylated genes (DMG), differentially expressed genes (DEG) or genes both differentially methylated and differentially expressed in the ED or EEM of IVP compared to IVV conceptuses. Results demonstrated that identified critical ontological terms for the ED (such as somitogenesis, mesoderm formation, gastrulation) and the BMP and Wnt signaling pathways were enriched among hypermethylated DMG, down-regulated DEG, and genes hypermethylated in the promoter and inhibited in expression, in the ED of IVP embryos. Genes hypermethylated in the promoter and inhibited in expression in the EEM of IVP conceptuses were involved in epigenetic regulation. In conclusion, the in vitro process alters the development of main linage tissues in the pre-implantation embryo, even after interaction with the maternal environment.]]> Wed, 31 Dec 1969 19:00:00 EST How do threatened plant species with low genetic diversity respond to environmental stress? Insights from comparative conservation epigenomics and phenotypic plasticity. Williams BR, Miller AJ, Edwards CE
Mol Ecol Resour (Jul 2025)

Many threatened plants have low genetic diversity, which may reduce their capacity for genetically based adaptation, increasing their extinction risk. Non-genetic variation (e.g. epigenomic modifications such as DNA methylation) and plasticity may facilitate the persistence of threatened plants, yet are rarely incorporated into conservation assessments. We present a case study investigating variation and plasticity in DNA methylation and phenotypic traits in four genetically depauperate species of Leavenworthia (Brassicaceae), including one widespread species and one asexual, threatened species. We grew individuals from several maternal lines and populations per species in contrasting watering treatments, measured phenotypic traits and analysed DNA methylation using whole-genome bisulphite sequencing. We addressed four questions: (1) How do patterns of DNA methylation differ within and among species? (2) Within species, how do phenotypic traits and patterns of DNA methylation vary in response to drought? (3) Does variation in DNA methylation correspond to phenotypic variation? (4) What are the implications for conservation? We found that taxa were epigenomically distinct and that each species exhibited variation in DNA methylation among populations that could be relevant for conservation. Within species, the DNA methylation response to environmental stress corresponded to its phenotypic response. Species differed in their DNA methylation and phenotypic responses to environmental stress, with the extent of plasticity possibly related to species geographic range size. We also found phenotypic and DNA methylation variation in the asexual, threatened species that may be relevant for conservation. Our results suggest that variation in DNA methylation may promote the persistence of genetically depauperate threatened plants, highlighting its potential as a novel conservation target to reduce extinction risk.]]> Wed, 31 Dec 1969 19:00:00 EST Differential methylation patterns in cord blood associated with prenatal exposure to neighborhood crime: an epigenome-wide association study and regional analysis. Martin CL, Chen J, D'Alessio AS, Ward-Caviness CK, Ye A, Lodge EK, Ghastine L, Dhingra R, Jima DD, Murphy SK, Hoyo C
Epigenetics (Dec 2025)

Exposure to prenatal social stressors during pregnancy is associated with adverse birth outcomes and has been linked to epigenetic changes in DNA methylation (DNAm); however, less understood is the effect of neighborhood-level stressors like crime during pregnancy on offspring DNAm. Using data from the Newborn Epigenetic Study, we conducted epigenome-wide and regional analyses of the association between exposure to neighborhood crime and DNAm in offspring cord blood using Illumina's HumanMethylation450k BeadChip among 185 mother-offspring pairs. Prenatal exposure to neighborhood crime at the census block group level was mapped to participants' residential addresses during the gestational window from the date of last menstrual period to delivery. Models for the epigenome-wide and regional analyses were adjusted for maternal age, race/ethnicity, education, smoking, cell-type composition, and offspring sex. Genetic influence and gene expression enrichment were assessed using methylation quantitative trait loci (mQTLs) and expression quantitative trait methylation (eQTMs) analyses. Functional enrichment was determined using Gene Ontology and KEGG databases. We did not find evidence of epigenome-wide associations between prenatal neighborhood crime exposure and DNAm; however, we identified nine differentially methylated regions (DMRs) comprising 51 CpG sites associated with neighborhood crime. CpG sites within significant differentially methylated regions were associated with mQTLs at birth and eQTMs upon further examination. KEGG analysis identified a significant Th1 and Th2 cell differentiation pathway. Our results suggest potential links between prenatal neighborhood crime exposure and offspring DNAm; however, additional research is needed in larger cohorts across wider geographic areas to confirm our results.]]> Wed, 31 Dec 1969 19:00:00 EST Assessment of the histone mark-based epigenomic landscape in human myometrium at term pregnancy. Wu SPS, Quiroz E, Wang T, Montague Redecke SG, Xu X, Lin L, Anderson ML, DeMayo FJ
Elife (Jun 2025)

The myometrium plays a critical role during pregnancy as it is responsible for both the structural integrity of the uterus and force generation at term. Emerging studies in mice indicate a dynamic change of the myometrial epigenome and transcriptome during pregnancy to ready the contractile machinery for parturition. However, the regulatory systems underlying myometrial gene expression patterns throughout gestation remain largely unknown. Here, we investigated human term pregnant nonlabor myometrial biopsies for transcriptome, enhancer histone mark cistrome, and chromatin conformation pattern mapping. More than thirty thousand putative enhancers with H3K27ac and H3K4me1 double positive marks were identified in the myometrium. Enriched transcription factor binding motifs include known myometrial regulators AP-1, STAT, NFkB, and PGR among others. Putative myometrial super enhancers are mostly colocalized with progesterone receptor-occupying sites and preferentially associated with highly expressing genes, suggesting a conserved role of PGR in regulating the myometrial transcriptome between species. In human myometrial specimens, inferred PGR activities are positively correlated with phospholipase C like 2 () mRNA levels, supporting that PGR may act through this genomic region to promote expression. PGR overexpression facilitated gene expression in myometrial cells. Using CRISPR activation, we assessed the functionality of a PGR putative enhancer 35 kilobases upstream of the contractile-restrictive gene . In summary, the results of this study serve as a resource to study gene regulatory mechanisms in the human myometrium at the term pregnancy stage for further advancing women's health research.]]> Wed, 31 Dec 1969 19:00:00 EST use capsules, transporters, mobile genetic elements, and other evolutionary adaptations to survive antibiotics exposure in the absence of resistance genes. Mmatli M, Mbelle NM, Fourie B, Osei Sekyere J
Virulence (Dec 2025)

Whole-genome sequencing, transcriptomic profiling, and epigenomic analyses were performed. Phenotypic assays were used to evaluate the effects of various inhibitors on antibiotic susceptibility, while bioinformatic pipelines were used to characterize resistance determinants, virulence factors, and mobile genetic elements (MGEs).]]> Wed, 31 Dec 1969 19:00:00 EST Improving polygenic prediction from whole-genome sequencing data by leveraging predicted epigenomic features. Zeng W, Guo H, Liu Q, Wong WH
Proc Natl Acad Sci U S A (Jun 2025)

Polygenic risk scores (PRS) are essential tools for estimating individual susceptibility to complex diseases by aggregating the effects of many genetic variants. With the advent of whole-genome sequencing (WGS), rare and de novo variants can now be detected at scale, presenting new opportunities to enhance PRS performance. Additionally, regulatory mechanisms that govern gene expression play a critical role in disease manifestation, suggesting further potential for improvement. However, most existing PRS methods are not well-equipped to incorporate nonlinear variant effects, rare variant contributions, or regulatory context. To address these limitations, we developed Epi-PRS, a novel framework that leverages large language models (LLMs) to impute cell-type-specific epigenomic signals from personal diploid genotypes. These imputed signals act as informative intermediates between genotype and phenotype, allowing for more accurate modeling of variant impact. Our simulation studies demonstrate that Epi-PRS improves predictive accuracy by incorporating nonlinear relationships, rare variant effects, and regulatory information across large genomic regions. When applied to real data from the UK Biobank, Epi-PRS significantly outperforms existing PRS approaches in predicting risk for both breast cancer and type 2 diabetes. These results underscore the advantages of integrating WGS data, epigenomic context, and advanced LLMs framework to enhance both the predictive power and interpretability of PRS. Overall, Epi-PRS represents a promising step toward more precise and biologically informed disease risk prediction, with broad implications for advancing personalized medicine and understanding complex genetic architectures.]]> Wed, 31 Dec 1969 19:00:00 EST Host-microbe multi-omics and succinotype profiling have prognostic value for future relapse in patients with inflammatory bowel disease. O'Sullivan J, Patel S, Leventhal GE, Fitzgerald RS, Laserna-Mendieta EJ, Huseyin CE, Konstantinidou N, Rutherford E, Lavelle A, Dabbagh K, DeSantis TZ, Shanahan F, Temko A, Iwai S, Claesson MJ
Gut Microbes (Dec 2025)

Crohn's disease (CD) and ulcerative colitis (UC) are chronic relapsing inflammatory bowel disorders (IBD), the pathogenesis of which is uncertain but includes genetic susceptibility factors, immune-mediated tissue injury and environmental influences, most of which appear to act via the gut microbiome. We hypothesized that host-microbe alterations could be used to prognostically stratify patients experiencing relapses up to four years after endoscopy. We therefore examined multiple omics data, including published and new datasets, generated from paired inflamed and non-inflamed mucosal biopsies from 142 patients with IBD (54 CD; 88 UC) and from 34 control (non-diseased) biopsies. The relapse-predictive potential of 16S rRNA gene and transcript amplicons (standing and active microbiota) were investigated along with host transcriptomics, epigenomics and genetics. While standard single-omics analysis could not distinguish between patients who relapsed and those that remained in remission within four years of colonoscopy, we did find an association between the number of flares and a patient's succinotype. Our multi-omics machine learning approach was also able to predict relapse when combining features from the microbiome and human host. Therefore multi-omics, rather than single omics, better predicts relapse within 4 years of colonoscopy, while a patient's succinotype is associated with a higher frequency of relapses.]]> Wed, 31 Dec 1969 19:00:00 EST DNA methylation mechanisms in the maturing and ageing oocyte. Caniçais C, Vasconcelos S, Santos F, Dória S, Marques CJ
Epigenetics Chromatin (Jun 2025)

Oocyte maturation involves both nuclear and cytoplasmic processes that are critical for the acquisition of oocyte competence. Granulosa cells, surrounding the oocyte, play a pivotal role in the maturation process, with mechanisms such as cAMP signaling significantly influencing oocyte development. Epigenetic mechanisms - including DNA methylation and its oxidative derivatives, histone post-translational modifications and chromatin remodeling - interfere with the accessibility of transcription factors to regulatory regions of the genome, such as promoter regions of genes, hence generally regulating gene expression profiles; however, in oocytes, transcription is largely independent of DNA methylation patterns. Here we highlight epigenetic reprogramming events occurring during oocyte development and ageing, focusing on the establishment of gamete-specific epigenetic marks, including DNA modifications at imprinted regions, and age-related epigenetic changes. We focus on the mechanisms of DNA methylation and demethylation during mouse and human oocyte maturation, alongside an exploration of how ageing impacts the oocyte epigenome and its implications for reproductive success. By providing a comprehensive analysis of the role of epigenetics in oocyte development and maturation, this review addresses the importance of comprehending these processes to enhance in vitro fertilization treatments and improve reproductive outcomes.]]> Wed, 31 Dec 1969 19:00:00 EST Multigenerational exposure to DEHP drives dysregulation of imprinted gene Snurf to impair decidualization. Tan L, Gao R, Su Y, Zhang Y, Geng Y, Liu Q, Ma Y, Chen X, Li F, He J
J Hazard Mater (Aug 2025)

Phthalate-induced female reproductive health issues, particularly those related to di (2-ethylhexyl) phthalate (DEHP), are growing global concerns. Although most studies have focused on single-generation exposure, studies on prolonged DEHP exposure across multiple generations are limited. This study assessed the effects of multigenerational DEHP exposure on endometrial decidualization, which is crucial for embryo implantation. The results showed that sustained DEHP exposure over three generations exacerbated decidualization injury and led to adverse pregnancy outcomes. RNA sequencing revealed upregulation of the imprinted gene Snurf in the decidua, with changes that may not depend on alterations in DNA methylation. Knockdown of Snurf significantly alleviated in vitro decidualization deficiency induced by mono(2-ethylhexyl) phthalate (MEHP), the biologically active metabolite of DEHP. Proteomic analysis and the AlphaFold 3 algorithm indicated that Stn1 is a downstream target of Snurf, with silencing Stn1 resensitizing Snurf-knockdown stromal cells to MEHP. Human decidual stromal cells (hDSCs) from healthy participants showed sensitivity to MEHP, with the inhibition of decidualization. Epidemiological data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) indicated a positive association between DEHP exposure and female infertility. This study highlighted the cumulative toxic effects of multigenerational DEHP exposure on female reproduction and revealed the contribution of imprinted genes.]]> Wed, 31 Dec 1969 19:00:00 EST The myoblast methylome: multiple types of associations with chromatin and transcription. Sen S, Lacey M, Baribault C, Ponnaluri VKC, Esteve PO, Ehrlich KC, Meletta M, Pradhan S, Ehrlich M
Epigenetics (Dec 2025)

Epigenetic changes are implicated in development, repair, and physiology of postnatal skeletal muscle (SkM). We generated methylomes for human myoblasts (SkM progenitor cells) and determined myoblast differentially methylated regions (DMRs) for comparison to the epigenomics and transcriptomics of diverse cell types. Analyses were from global genomic and single-gene perspectives and included reporter gene assays. One atypical finding was the association of promoter-adjacent hypermethylation in myoblasts with transcription turn-on, but at downmodulated levels, for certain genes (., and ). In contrast, brain-specific was in repressed chromatin and silent in most cell types but linked to hypermethylated DMRs specifically in myoblasts. The -linked DMRs might be needed because of the overlapping or nearby binding of myogenic differentiation protein 1 (MYOD). We found genome-wide overlap of DMRs with MYOD or CCCTC-binding factor (CTCF) binding sites in myoblasts that is consistent with the importance of MYOD, as well as CTCF, in organizing myoblast transcription-enhancing chromatin interactions. We also observed some gene upregulation correlated with a special association of regional DNA hypomethylation with H3K36me3, H3K27ac, and H3K4me1 enrichment. Our study highlights unusual relationships between epigenetics and gene expression that illustrate the interplay between DNA methylation and chromatin epigenetics in the regulation of transcription.]]> Wed, 31 Dec 1969 19:00:00 EST NSD1 mutation status determines metabolic inhibitor sensitivity in head and neck squamous cell carcinomas by regulating mitochondrial respiration. Tang S, Wang Q, Wang Z, Cai L, Pan D, Li J, Chen Q, Zhou Y, Shen YQ
J Pathol (Jul 2025)

Head and neck squamous cell carcinomas (HNSCCs) are the most common malignant tumors in the head and neck region, characterized by a high recurrence rate and early metastasis. Despite advances in treatment, patient outcomes and prognosis remain poor, highlighting the urgent need for new therapeutic strategies. Recent research has increasingly focused on targeting glucose metabolism as a therapeutic strategy for cancer, revealing multiple promising targets and potential drugs. However, the metabolic heterogeneity among tumors leads to variable sensitivity to metabolic inhibitors in different patients, limiting their clinical utility. In this study, we employed bioinformatics analysis, cell experiments, animal models, and multi-omics approaches to reveal differences in glucose metabolism phenotypes among HNSCC patients and elucidated the underlying molecular mechanisms driving these differences. Our findings showed that NSD1 mutation status affects the glucose metabolism phenotype in HNSCC, with NSD1 wild-type HNSCC exhibiting higher mitochondrial respiration and NSD1 mutant HNSCC showing weaker mitochondrial respiration but enhanced glycolysis. We further demonstrated that NSD1 regulates mitochondrial respiration in HNSCC via epigenetic modulation of the TGFB2/PPARGC1A signaling axis. Additionally, we found that NSD1 wild-type HNSCC is more sensitive to mitochondrial respiration inhibitors, whereas NSD1 mutant HNSCC shows increased sensitivity to glycolysis inhibitors. In summary, we found that NSD1 can epigenetically regulate the TGFB2/PPARGC1A axis to modulate mitochondrial respiration and sensitivity to metabolic inhibitors in HNSCC. These findings suggest a novel strategy for selecting metabolic inhibitors for HNSCC based on the NSD1 gene status of patients. © 2025 The Pathological Society of Great Britain and Ireland.]]> Wed, 31 Dec 1969 19:00:00 EST The roles of maternal one-carbon metabolism and placental imprinted gene expression in placental development and somatic growth in a longitudinal birth cohort. Gutherz OR, Li Q, Deyssenroth M, Wainwright H, Jacobson JL, Meintjes EM, Chen J, Jacobson SW, Carter RC
Placenta (Jun 2025)

One-carbon nutrients and imprinted genes both play critical roles in placental development and somatic growth. We aimed to examine (1) the impact of maternal one-carbon nutrition on placental imprinted gene expression, placental development, and infant growth and (2) interactions between one-carbon nutrients and imprinted genes in placental development and infant growth.]]> Wed, 31 Dec 1969 19:00:00 EST Advances and applications of multiomics technologies in precision diagnosis and treatment for gastric cancer. Shen K, Hu C, Zhang Y, Cheng X, Xu Z, Pan S
Biochim Biophys Acta Rev Cancer (Jul 2025)

Gastric cancer (GC), one of the most prevalent malignancies worldwide, is distinguished by extensive genetic and phenotypic heterogeneity, posing persistent challenges to conventional diagnostic and therapeutic strategies. The significant global burden of GC highlights an urgent need to unravel its complex underlying mechanisms, discover novel diagnostic and prognostic biomarkers, and develop more effective therapeutic interventions. In this context, this review comprehensively examines the transformative roles of cutting-edge technologies, including radiomics, pathomics, genomics, transcriptomics, epigenomics, proteomics, and metabolomics, in advancing precision diagnosis and treatment for GC. Multiomics data analysis not only deepens our understanding of GC pathogenesis and molecular subtypes but also identifies promising biomarkers, facilitating the creation of tailored therapeutic approaches. Additionally, integrating multiomics approaches holds immense potential for elucidating drug resistance mechanisms, predicting patient outcomes, and uncovering novel therapeutic targets, thereby laying a robust foundation for precision medicine in the comprehensive management of GC.]]> Wed, 31 Dec 1969 19:00:00 EST Advancing omics technologies in acute respiratory distress syndrome: paving the way for personalized medicine. Al-Husinat L, Araydah M, Al Sharie S, Azzam S, Battaglini D, Alrababah A, Haddad R, Al-Asad K, Dos Santos CC, Schultz MJ, Cruz FF, Silva PL, Rocco PRM
Intensive Care Med Exp (Jun 2025)

Despite advances in critical care, acute respiratory distress syndrome (ARDS) remains a potentially life-threatening condition with high mortality. The heterogeneous nature of ARDS, caused by diverse etiologies, poses considerable challenges to accurate diagnosis, treatment, and prognosis. Conventional methods often fail to elucidate the pathophysiology of ARDS, thus limiting therapeutic efficacy. However, recent advances in omics technologies, including genomics, transcriptomics, proteomics, metabolomics, lipidomics, and epigenomics, have provided deeper insights into ARDS mechanisms. Genomic studies have identified genetic variants associated with ARDS susceptibility, such as polymorphisms in genes encoding angiotensin-converting enzyme, surfactant proteins, toll-like receptor 4, interleukin-6, Fas/FasL, and vascular endothelial growth factor, offering potential therapeutic targets. Transcriptomic and proteomic reveal distinct biomarker profiles associated with ARDS pathogenesis, including dysregulated inflammatory signaling, epithelial and endothelial barrier dysfunction, and compromised immune responses. Metabolomics has highlighted biomarkers, such as phenylalanine and choline, aiding in severity assessment, subphenotype stratification, and treatment response prediction. Lipidomics has uncovered disruptions in lipid metabolism, including altered phospholipids, sphingolipids, and eicosanoids, with key lipid species such as lysophosphatidylcholine and ceramide emerging as biomarkers for severity and outcomes. Epigenomics explores DNA methylation, histone modifications, and non-coding RNAs, revealing their role in regulating inflammation, immune responses, and tissue repair in ARDS. These epigenetic changes hold promise for biomarker discovery and personalized therapy. Integrating these omics technologies advances our understanding of ARDS pathophysiology, enabling precision medicine approaches. This review examines the latest advancements in omics research related to ARDS, emphasizing its role in developing personalized diagnostics and therapeutic strategies to improve disease monitoring, prognosis, and treatment outcomes.]]> Wed, 31 Dec 1969 19:00:00 EST Histone modifications as molecular drivers of cardiac aging: Metabolic alterations, epigenetic mechanisms, and emerging therapeutic strategies. Alrumaihi F, Al-Doaiss AA, Ullah F, Alwanian WM, Alharbi HO, Alassaf FA, Alfifi SM, Alshabrmi FM, Aba Alkhay FF, Alatawi EA
Curr Probl Cardiol (Jul 2025)

Cardiac aging represents a complex pathophysiological process characterized by progressive metabolic recombination and functional dedifferentiation of cardiac cellular components. Despite advancements in cardiovascular medicine, a critical research gap persists in understanding the precise epigenetic mechanisms that drive age-related cardiac dysfunction. This comprehensive review elucidates the pivotal role of histone modifications-including methylation, acetylation, and phosphorylation-in orchestrating the molecular landscape of cardiac aging. Significant gaps remain in our understanding of site-specific histone modification impacts on cardiac function, the intricate crosstalk between different histone marks, and their integration with metabolic alterations that characterize the aging myocardium. Current evidence reveals a dynamic epigenetic signature in aged cardiac tissue, typically featuring increased transcriptional activation markers alongside decreased repressive marks, though context-dependent variations exist. This review explores how histone modifications influence critical pathways governing mitochondrial dysfunction, DNA damage repair, inflammation, and fibrosis in aging hearts. Innovative therapeutic approaches targeting specific histone-modifying enzymes promise to mitigate age-related cardiac deterioration, potentially revolutionizing treatment paradigms for cardiovascular diseases in aging populations. Addressing these knowledge gaps requires multidimensional approaches that integrate epigenomics with functional assessment of cardiac performance.]]> Wed, 31 Dec 1969 19:00:00 EST Prenatally Detected Maternally Inherited Partial Duplication of 11p15.5 ICR1 Results in Phenotypes Overlapping Russell-Silver Syndrome in Infancy. Thomas-Wilson A, Ganapathi M, Harkavy N, Schwanke C, Giordano J, Elias AF, Wapner RJ, Jobanputra V
Prenat Diagn (Jun 2025)

Differentially methylated regions (DMRs) in certain areas of the genome are subject to genomic imprinting. DMRs at chromosome 11p15.5 are associated with Beckwith-Wiedemann syndrome (BWS) and Russell-Silver Syndrome (RSS), two growth disorders with opposite phenotypes. We identified a maternally inherited duplication containing part of the 11p15 DMR in a non-anomalous fetus in first trimester using genome sequencing (GS). The ∼281kb duplication at 11p15.5 contains the entire imprinting control region 1 (ICR1) and the H19 gene but lacks the IGF2 gene and the imprinting control region 2 (ICR2). Methylation studies revealed hypomethylation of ICR1 in fetal cells as well as in the mother (leukocytes), who had a history of feeding difficulties in infancy and short stature. The duplication was inherited from the asymptomatic maternal grandmother of the fetus, who showed hypermethylation of ICR1 in leukocytes suggesting paternal inheritance. The fetus developed decelerating growth in late gestation and phenotypes overlapping those of RSS were noted in infancy. This study adds to the limited literature on partial duplications of the 11p15.5 region and their associated phenotypes, underscoring the efficacy of GS in cases involving DMRs associated with imprinting disorders.]]> Wed, 31 Dec 1969 19:00:00 EST Broadening the Nicotiana benthamiana research toolbox through the generation of dicer-like mutants using CRISPR/Cas9 approaches. Bardani E, Katsarou K, Mitta E, Andronis C, Å tefková M, Wassenegger M, Kalantidis K
Plant Sci (Jul 2025)

RNA silencing in plants plays a pivotal role in various biological processes, including development, epigenetic modifications and stress response. Key components of this network are Dicer-like (DCL) proteins. Nicotiana benthamiana encodes four DCLs, each responsible for the generation of distinct small RNA (sRNA) populations, which regulate different functions. However, elucidating the precise role of each DCL has been proven challenging, as overlapping functions exist within DCLs. In our present study, we have successfully generated dcl2, dcl3 and dcl4 homozygous mutants, employing two different CRISPR/Cas9 approaches. The first approach is based on a transgene-mediated delivery of the single-guide RNA (sgRNA), while the second approach employs a viral vector for sgRNA delivery. By utilizing a suite of screening techniques, including polymerase chain reaction (PCR), T7 endonuclease I (T7E1) assay, high-resolution melt analysis (HRMA) and DNA sequencing, we successfully generated dcl2, dcl3 and dcl4 homozygous mutants harboring identical mutations in every allele. To evaluate these dcl mutants, we examined their sRNA profiles and phenotypes. We further have indications that homozygous mutations of a gene do not always lead to the desired loss-of-function, highlighting the importance of mutant evaluation. dcl mutants represent invaluable tools to explore how overlapping silencing pathways are connected to essential plant functions, including development, stress responses and pathogen defense. Additionally, they hold potential for biotechnological applications, such as crop improvement and gene silencing tools. We anticipate that our study will make significant contributions to enhance understanding of the role of DCLs in plants.]]> Wed, 31 Dec 1969 19:00:00 EST spaMGCN: a graph convolutional network with autoencoder for spatial domain identification using multi-scale adaptation. Zhang T, Zhang H, Zhao Z, Shao S, Jiang Y, Zhang X, Wang G
Genome Biol (Jun 2025)

Spatial domain identification is crucial in spatial transcriptomics analysis. Existing methods excel with continuous and clustered distributions but struggle with discrete ones. We present spaMGCN, an innovative approach specifically designed for identifying spatial domains, especially in discrete tissue distributions. By integrating spatial transcriptomics and spatial epigenomic data through an autoencoder and a multi-scale adaptive graph convolutional network, spaMGCN outperforms baseline methods. Our evaluations demonstrate its effectiveness in recognizing discrete T cell zones in mouse spleens and follicular cells in human lymph nodes, as well as effectively distinguishing capsule structures from surrounding tissues.]]> Wed, 31 Dec 1969 19:00:00 EST Development and validation of a machine learning prognostic model based on an epigenomic signature in patients with pancreatic ductal adenocarcinoma. Zaccaria GM, Altini N, Mongelli V, Marino F, Bevilacqua V
Int J Med Inform (Jul 2025)

In Pancreatic Ductal Adenocarcinoma (PDAC), current prognostic scores are unable to fully capture the biological heterogeneity of the disease. While some approaches investigating the role of multi-omics in PDAC are emerging, the analysis of methylation data is under exploited.]]> Wed, 31 Dec 1969 19:00:00 EST Decoding human cardiovascular development and disease through single-cell transcriptomic and epigenomic profiling. Dunkenberger L, Li DY, Karakikes I, Quertermous T
Trends Cell Biol (Jun 2025)

Concomitant progress in the fields of microfluidics, microscale molecular biology, next-generation sequencing, and analytical methods for whole transcriptomic datasets has transformed our ability to understand complex cellular state changes at the single-cell level. New cell types have been discovered and cell transition states and intermediate phenotypes have been characterized across diverse developmental and disease contexts. More recently, integrating transcriptomic and epigenomic data has dramatically extended our understanding of transcriptional regulons and gene regulatory networks (GRNs) that determine gene expression and individual cellular phenotypes. Applied to cardiac biology, combined transcriptomic and epigenomic profiling has allowed the characterization of the developmental trajectories and molecular mechanisms that give rise to the diverse cell lineages of the adult heart and contribute to the pathogenesis of genetic diseases. In this review, we present the latest methodological innovations, discuss the computational strategies for multiomic data integration, and highlight how these advances are reshaping our undestanding of heart development and disease mechanisms.]]> Wed, 31 Dec 1969 19:00:00 EST