'; ?> 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 Fri, 05 Jun 2026 14:14:46 EDT Fri, 05 Jun 2026 14:14:46 EDT jirtle@radonc.duke.edu james001@jirtle.com Epigenetic reprogramming of tissue-resident memory T cells in chronic inflammatory disorders and implications for targeted therapies. Ling C, Isleem HF, Tejani GG
Epigenomics (Jun 2026)

Tissue-resident memory T (TRM) cells play a role in causing long-term tissue injury in chronic inflammatory diseases via pathological epigenetic reprogramming. Nevertheless, the epigenetic processes that cause this malfunction have not been well defined.]]> Wed, 31 Dec 1969 19:00:00 EST Single-cell mapping of regulatory DNA-protein interactions. Chi WY, Yoon SH, Goksel E, Mekerishvili L, Pelt J, Lin Y, Prieto T, Zinno J, Ganesan S, Potenski C, Izzo F, Landau DA, Raimondi I
Cell (Jun 2026)

Gene expression is controlled by transcription factors (TFs), whose genome binding is shaped by chromatin accessibility and histone modifications, yet mapping these interactions, particularly those with weak affinity or a transient nature, in single cells remains technically challenging. To address this gap, we developed docking and deamination followed by sequencing (D&D-seq), a single-cell immuno-tethering technology for profiling DNA-protein interactions. D&D-seq couples an antibody-binding nanobody to a cytosine base editor, a combination that enables detection of weak or transient factor binding through targeted cytosine-to-uracil editing at protein-bound genomic sites. This approach is compatible with standard single-cell multi-omic workflows and therefore allows integrated analyses of gene regulation. Using assay for transposase-accessible chromatin using sequencing (ATAC-seq) and single-cell ATAC-seq (scATAC-seq), we assessed chromatin accessibility as a functional readout of TF activity, and by coupling D&D-seq with whole-genome sequencing, we captured CTCF binding in both active and inactive chromatin compartments.]]> Wed, 31 Dec 1969 19:00:00 EST Interactions between nutrition and the epigenome: how can it be harnessed for public health? Anastasopoulou M, Dereki I, Sgourou A, Lagoumintzis G
Future Sci OA (Dec 2026)

A substantial body of evidence shows that dietary habits influence gene expression and epigenetic processes, holding significant implications for public health policies. Epigenetic modifications are increasingly associated with metabolic state, disease risk, and biological aging. Translating mechanistic results into scalable, efficient nutritional epigenetics treatments is difficult.]]> Wed, 31 Dec 1969 19:00:00 EST Molecular basis of precision nutrition: Food components, microbiome-derived metabolites, and multi-omics modeling. Rahimah S, Tallei TE, Savitri M, Yamada C, Kim HJ, Choi M, Park MN, Ophinni Y, Kim B
Food Chem (Oxf) (Jun 2026)

Metabolic disorders, including obesity, type 2 diabetes, metabolic syndrome, and fatty liver disease, reflect multifactorial interactions among diet, host genetics, the environment, and the gut microbiome. However, conventional population-level dietary guidance often fails to capture the marked interindividual variability in metabolic responses to identical foods and nutrients. Precision nutrition has therefore emerged as an integrative paradigm that combines genomics, epigenomics regulation, microRNA-mediated control, and microbiome profiling to refine dietary recommendations, with a growing emphasis on targeted functional food-based strategies for metabolic health. This narrative review synthesizes the mechanistic foundations of precision nutrition, emphasizing how functional foods and their bioactive constituents engage nutrient-sensing and regulatory pathways that connect dietary exposures to gene regulation and downstream metabolic phenotypes. We summarize evidence for diet-gene interactions at key metabolic loci, epigenetic programming shaped by early-life nutrition, and diet-responsive microRNAs as candidate biomarkers of nutritional response. We further examine microbiome-derived signaling, specifically short-chain fatty acids and bile-acid metabolism within the gut-liver axis, as a major route by which functional dietary components can influence host pathways and condition metabolic outcomes. We highlight insights from large cohorts and controlled metabolic profiling studies and discuss enabling methodological advances, including multi-omics integration, causal inference, and machine learning models for response prediction. Key limitations remain, notably incomplete reproducibility, heterogeneity in exposure and outcome measurements, data governance challenges, and barriers to clinical implementation. In summary, precision nutrition provides a biologically grounded framework for personalized functional-food and dietary strategies, but robust validation and responsible translation are required before routine adoption.]]> Wed, 31 Dec 1969 19:00:00 EST Melatonin-enabled omics: understanding plant responses to single and combined abiotic stresses for climate-smart agriculture. Raza A, Li Y, Charagh S, Guo C, Zhao M, Hu Z
GM Crops Food (Dec 2026)

Climate change-driven single and combined abiotic stresses pose escalating threats to sustainable, climate-smart agriculture and global food security. Melatonin (MLT, a powerful plant biostimulant) has established noteworthy potential in improving stress tolerance by regulating diverse physiological, biochemical, and molecular responses. Therefore, this review delivers a comprehensive synopsis of MLT-enabled omics responses across genomics, transcriptomics, proteomics, metabolomics, miRNAomics, epigenomics, phenomics, ionomics, and microbiomics levels that collectively regulate plant adaptation to multiple abiotic stresses. We also highlight the crosstalk between these omics layers and the power of integrated multi-omics (panomics) approaches to harness the complex regulatory networks underlying MLT-enabled stress tolerance. Lastly, we argue for translating these omics insights into actionable strategies through advanced genetic engineering and synthetic biology platforms to develop MLT-enabled, stress-smart crop plants.]]> Wed, 31 Dec 1969 19:00:00 EST Multi-ancestry transcriptome-wide association study reveals shared and population-specific genetic effects in Alzheimer disease. Sun X, Mews M, Wheeler NR, Benchek P, Gu T, Gomez L, Ray N, Reitz C, Naj AC, Below JE, Tosto G, Cornejo-Olivas M, Byrd GS, Feliciano-Astacio BE, Celis K, Rajabli F, Kunkle BW, Pericak-Vance MA, Haines JL, Griswold AJ, Bush WS
Am J Hum Genet (Jun 2026)

Alzheimer disease (AD) risk differs across ancestral populations, yet most genetic studies have focused on non-Hispanic White (NHW) cohorts. We conducted a multi-population transcriptome-wide association study (TWAS) using whole-blood RNA sequencing (RNA-seq) and genotype data from NHW (n = 235), African American (AA; n = 224), and Hispanic (HISP; n = 292) Multi-Ancestry Genomics, Epigenomics, and Transcriptomics of Alzheimer's (MAGENTA) participants. Using sum of shared single effects (SuShiE) for multi-population cis-eQTL fine-mapping, we identified credible sets for 8,748 genes, improving fine-mapping precision relative to analyses using fewer populations. cis-eQTL effects were largely shared across populations, with a subset showing population-specific regulation. We performed population-stratified TWAS of AD and inverse-variance-weighted meta-analysis, followed by gene-level TWAS fine-mapping (MA-FOCUS), prioritizing nine genes (false discovery rate [FDR] <0.05, posterior inclusion probability [PIP] >0.8), including established AD loci (BIN1, PTK2B, DMPK) with broadly consistent effects across populations. At BIN1, fine-mapped cis-eQTL variants used in the TWAS prediction model highlighted rs11682128, which is only modestly correlated with the genome-wide association study (GWAS) index SNP rs6733839 (r ≈ 0.34), demonstrating how integrating eQTL fine-mapping with TWAS can refine signals beyond sentinel GWAS variants. We also identified an association between COG4 expression and AD in NHW, implicating Golgi-related pathways. Using independent SuShiE-derived models from TOPMed MESA (PBMC), several signals replicated directionally across ancestries, with the strongest statistical support in NHW. Overall, multi-population eQTL fine-mapping improves model interpretability and helps resolve shared and population-specific regulatory mechanisms relevant to AD.]]> Wed, 31 Dec 1969 19:00:00 EST A cell type enrichment analysis tool for brain DNA methylation data (CEAM). Müller J, Laroche VT, Imm J, Weymouth L, Harvey J, Reijnders RA, Smith AR, van den Hove D, Lunnon K, Cavill R, Pishva E
Epigenetics (Dec 2026)

DNA methylation (DNAm) signatures are highly cell type-specific, yet most epigenome-wide association studies (EWAS) are performed on bulk tissue, potentially obscuring critical cell type-specific patterns. Existing computational tools for detecting cell type-specific DNAm changes are often limited by the accuracy of cell type deconvolution algorithms. Here, we introduce CEAM (Cell-type Enrichment Analysis for Methylation), a robust and interpretable framework for cell type enrichment analysis in DNA methylation data. CEAM applies over-representation analysis with cell type-specific CpG panels from Illumina EPIC arrays derived from nuclei-sorted cortical post-mortem brains from neurologically healthy aged individuals. The constructed CpG panels were systematically evaluated using both simulated datasets and published EWAS results from Alzheimer's disease, Lewy body disease, and multiple sclerosis. CEAM demonstrated resilience to shifts in cell type composition, a common confounder in EWAS, and remained robust across a wide range of differentially methylated positions, when upstream modeling of cell type composition was modeled with sufficient accuracy. Application to existing EWAS findings generated in neurodegenerative diseases revealed enrichment patterns concordant with established disease biology, confirming CEAM's biological relevance. The workflow is publicly available as an interactive Shiny app (https://um-dementia-systems-biology.shinyapps.io/CEAM/) enabling rapid, interpretable analysis of cell type-specific DNAm changes from bulk EWAS.]]> Wed, 31 Dec 1969 19:00:00 EST Multi-Omics Integration Into Adverse Outcome Pathway Framework: Principles, Progress, and Prospects for Next-Generation Toxicological Risk Assessment. Pamanji R, Prathiviraj R, Sivan G
Environ Mol Mutagen (Jun 2026)

The adverse outcome pathway (AOP) framework has emerged as an important tool in mechanistic toxicology, providing chemically agnostic representations of the causal biological sequence from molecular initiating events (MIEs) to apical adverse outcomes (AOs). Yet, traditional AOP construction has relied predominantly on siloed, single-layer biological data, limiting both the mechanistic resolution and quantitative utility of AOPs in regulatory risk assessment. The proliferation of multi-omics technologies, such as transcriptomics, proteomics, metabolomics, and epigenomics, and their single-cell counterparts, now offers new opportunities to populate, validate, and quantify AOP networks with rich, multi-scale molecular data. This review systematically examines how each omics layer contributes uniquely to AOP development and discusses emerging frameworks for their integration. We describe the mechanistic logic underpinning transcriptome-guided key event (KE) identification, proteomic confirmation of KE-to-KE relationships (KERs), metabolomics-based linkage to phenotypic outcomes, epigenomic annotation of persistent and transgenerational effects, and single-cell resolution approaches that dissolve the cell population averaging problem inherent in bulk assays. We further assess quantitative AOP (qAOP) strategies built on benchmark dose (BMD) modeling of omics data, with emerging evidence that transcriptomic points of departure (tPODs) derived from short-term exposures are concordant with chronic apical endpoints. Critical knowledge gaps are identified, including incomplete molecular annotation of KEs in AOP-Wiki, the absence of standardized multiomics bioinformatics pipelines, the underdevelopment of epigenomic and spatial transcriptomic AOP layers, and regulatory hurdles impeding the translation of omics-derived PODs into health-based guidance values (HBGVs). We conclude with a forward-looking framework and research priorities to accelerate the regulatory acceptance of multiomics-informed AOPs as tools for next-generation chemical risk assessment.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic research methods and animal models for intervertebral disc degeneration (Review). Cui X, Zeng L, Zhang W, Xi L, Wang R, Jia D, Safa , Feng H, Jia H
Mol Med Rep (Jul 2026)

Intervertebral disc degeneration (IVDD) is increasingly recognized as a systemic collapse of the epigenetic regulatory network, driven by cellular senescence and environmental stressors. The present review provides an overview of the epigenetic regulatory mechanisms governing IVDD, focusing on the dynamic interplay between DNA methylation, histone modifications, N6‑methyladenosine RNA methylation and the non‑coding RNA regulatory triad (microRNAs, long non‑coding RNAs and circular RNAs). The present study evaluates advanced research methodologies (ranging from site‑specific methylation typing and transposase accessible chromatin sequencing to single‑cell multi‑omics and artificial intelligence‑driven predictive modeling) that resolve the spatial and cellular heterogeneities of the degenerating disc niche. Furthermore, the translational constraints of current animal models were critically assessed, advocating for a strategic shift from acute needle‑puncture insults to physiologically relevant aging and genetically engineered progeroid models to better recapitulate human 'epigenetic drift'. Finally, the therapeutic potential of targeted epigenetic editing via CRISPR/dCas9 systems and the development of stimuli‑responsive nanocarriers for precision delivery are highlighted. By bridging methodological innovation with robust model selection, the present review offers a roadmap for transitioning molecular insights into clinical regenerative therapies for spinal health.]]> Wed, 31 Dec 1969 19:00:00 EST Global analyses of genomic and epigenomic influences on gene expression reveal as a major regulator of cardiac gene expression in response to catecholamine challenge during heart failure. Lahue C, Ravindran S, Dalal A, Avetisyan R, Rau CD
Epigenetics (Dec 2026)

Heart failure arises from maladaptive remodelling driven by genetic and epigenetic networks. Using a systems genetics framework, we mapped how DNA variants and CpG methylation shape cardiac transcriptomes during beta adrenergic stress in the Hybrid Mouse Diversity Panel, a cohort of over 100 fully inbred mouse strains. Expression QTLs (eQTLs), methylation QTLs (mQTLs) and methylation-driven eQTLs (emQTLs) were generated from over 13k expressed genes and 200k hypervariable CpGs in left ventricles. We discovered hundreds of regulatory 'hotspots' that control large portions of the genome, including several that regulate over 10% of the transcriptome and/or methylome. Approximately 16% of these hotspots overlapped with prior GWAS or EWAS signals. We focus on a hotspot on chromosome 12 and identify the serpine peptidase inhibitor , as the most likely driver gene in this hotspot. Experimental knockdown of in neonatal rat ventricular cardiomyocytes blunted hypertrophy induced by a variety of hypertrophic signals, while altering predicted target expression and modulating the activity of and . Together, these findings position as a major regulator of stress-responsive cardiac gene programs, highlighting how integration of genetic and epigenetic signals can pinpoint key drivers of heart failure.]]> Wed, 31 Dec 1969 19:00:00 EST Cholangiocyte biology in primary sclerosing cholangitis and other cholangiopathies: pathogenesis, clinical insights, and experimental tools. Jalan-Sakrikar N, Anwar AA, Ali A, Nasser-Ghodsi N, Felzen A, Huebert RC, LaRusso NF, O'Hara SP
Physiol Rev (Jul 2026)

Cholangiocytes are specialized epithelial cells that line the intrahepatic and extrahepatic biliary tree and play a critical role in bile modification, liver homeostasis, and response to injury. Cholangiocytes exhibit notable heterogeneity and plasticity, and their dysfunction is central to a spectrum of diseases targeting the bile ducts, collectively called cholangiopathies. These disorders include genetic, infectious, immune-mediated, and malignant diseases, with primary sclerosing cholangitis (PSC) representing one of the most complex and enigmatic of these disorders. PSC is a progressive, fibro-inflammatory disease of the bile ducts that is closely linked to inflammatory bowel disease, carries a heightened risk of cancer, and lacks any approved therapies. This review explores the biology of cholangiocytes, including their development, functional plasticity, and roles in secretion, absorption, and cellular signaling. We provide a detailed examination of cholangiopathies, particularly PSC, a complex cholangiopathy characterized by a paradoxical state of cholangiocyte senescence and hyperproliferation. We describe how immune cell dysfunction, the gut microbiome, genetic predispositions, and environmental factors converge to mediate PSC pathogenesis. We revisit the foundational technologies that empowered early discoveries and shaped the field as we know it today. We also explore how newer techniques such as organoid cultures, single-cell transcriptomics, epigenomics, and spatialomics have transformed our modern understanding of biliary pathophysiology. Finally, we provide an overview of existing rodent models of cholangiopathies and discuss their relevance to human disease. PSC remains therapeutically unaddressed, and thus ongoing multidisciplinary efforts are essential to developing targeted interventions. This review serves as a comprehensive resource for researchers and clinicians navigating the rapidly evolving landscape of cholangiocyte-centered liver disease research.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic Regulation of Nephrogenesis: From Waddington's Landscape to Adult Disease. Tortelote GG, El-Dahr SS
Am J Physiol Renal Physiol (Jun 2026)

The establishment of lifelong nephron endowment depends on the tightly coordinated regulation of nephron progenitor cell (NPC) self-renewal, lineage specification, and differentiation during kidney development. Conrad H. Waddington's developmental landscape provides a powerful conceptual framework for understanding how NPCs navigate sequential fate decisions toward mature renal epithelial identities. Within this paradigm, the topology of the landscape is actively shaped by epigenetic mechanisms, including DNA methylation, histone post-translational modifications, non-coding RNA-mediated gene regulation, and higher-order chromatin organization, which collectively control the timing, location, duration, and strength of gene expression programs that direct nephrogenesis. Under normal conditions, these epigenetic programs preserve progenitor competence while progressively stabilizing lineage commitment and nephron patterning. When disrupted, however, they impair progenitor plasticity, accelerate NPC pool depletion, and ultimately reduce nephron number. Such maladaptive epigenetic reprogramming establishes a mechanistic link between adverse intrauterine environments and lifelong susceptibility to hypertension and chronic kidney disease. In this review, we revisit Waddington's landscape in the context of renal development and integrate emerging insights from developmental biology, cell metabolism, and epigenomics to examine how early-life environmental perturbations durably reshape the nephrogenic program and increase the risk of adult-onset kidney disease.]]> Wed, 31 Dec 1969 19:00:00 EST The transformative role of single-cell analysis in multifactorial disorders research. Wang CY, Ko CC, Kumar S, Xuan DTM, Lin HR, Lee YK, Nguyen NUN, Yang PM, Solomon DD
Methods (Jul 2026)

Multifactorial inherited disorders (MIDs) arise from complex interactions between polygenic risk and environmental exposures, presenting major challenges for mechanistic discovery, patient stratification, and targeted therapy development. While traditional approaches like genome-wide association studies (GWAS) and bulk omics profiling have identified broad associations, they often struggle to resolve the cellular context in which these interactions drive pathogenesis.Emergingsingle-cell technologies now offer unprecedented resolution to dissect tissue heterogeneity, define rare or transient disease-relevant cell states, and map dynamic trajectories across tissues and disease stages. This reviewprovides a comprehensive synthesis ofcurrent single-cell methodologies including transcriptomic, epigenomic, proteomic, and spatial techniques and their application to MID research. We explore how these toolsare revealingcell-type-specific regulatory circuits,contextualizingthe functional impact of inherited risk variants, andelucidatingcellular responses to environmental perturbations.We propose thatintegrating single-cell multi-omics data is critical for illuminating the mechanistic basis of complex traits and for advancing biomarker discovery. However, significant challenges remain, including technical variability, limited cohort scalability, difficulties in multi-modal data integration, and a lack of standardized analytical workflows for polygenic diseases. Overcoming these barriers will require harmonized study designs, robust computational frameworks, and the incorporation of longitudinal and environmental exposure data.Ultimately, we conclude thatsingle-cell analysis is poised to transform MID research, offering a powerful new paradigm for mechanistic insight, therapeutic innovation, and the realization of precision medicine.]]> Wed, 31 Dec 1969 19:00:00 EST Methods toward Single-Cell Total-Analysis. Zhang Q, Liao W, Lin L, Li XJ, Lin J, Song Y, Hou Y, Lin JM
Chem Rev (Jun 2026)

Single-cell total-analysis aims to bridge the gap between cellular molecular makeup and functional phenotype, deciphering how genomic, transcriptomic, proteomic, and metabolic networks orchestrate phenotypic outcomes. Despite rapid omics advances, a critical disconnect persists: nucleic acid-based analyses (genomics, epigenomics, transcriptomics) are mature, while proteomic/metabolomic profiling is incomplete, and comprehensive phenomics (the direct readout of cellular function) lags due to dynamic cellular complexity. This raises a core question: how to transcend isolated molecular layers to capture the ″molecular-phenotypic correlation″ in single cells? Multimodal integration progresses but is constrained by technical incompatibilities, throughput-depth trade-offs, and poor temporal resolution. This review examines advances in five core omics domains, identifies bottlenecks, analyzes multiomics coanalysis strategies, and outlines a roadmap for true single-cell total-analysis, emphasizing breakthrough approaches to unify molecular and phenotypic landscapes. We propose that true single-cell total-analysis is defined not by the accumulation of multiomic molecular layers, but by the direct establishment of phenotype-component correlations within the same individual cell.]]> Wed, 31 Dec 1969 19:00:00 EST TiSMeD: A tissue-specific methylation and expression database for biomarker and translational applications. Cheng J, Lin Z, Wu L, Li Q, Yin H, Wang H, Chen H, Chen X, Ji ZL
Mol Ther Nucleic Acids (Jun 2026)

Tissue-specific methylation sites (TSMs) are important epigenetic features associated with gene regulation, tissue development, and disease pathogenesis. However, the lack of comprehensive and reliable resources for TSMs restricts advancements in epigenetic and translational research. We present TiSMeD (http://www.bio-add.org/TiSMeD/), a multi-omics database integrating 6,782 DNA methylation, 16,894 transcriptome, and 241 proteome profiles across 48 normal human tissues. Using a scoring framework based on SPM and Tscore, we identified 67,427 high-confidence TSMs, 4,607 tissue-specific genes, and 2,833 tissue-specific proteins, along with over 11 million housekeeping methylation sites. TiSMeD enables interactive exploration and data retrieval, supporting biomarker discovery and disease research. We demonstrate its utility in tracing the tissue-of-origin of cell-free DNA (cfDNA), prioritizing 1,849 cancer biomarkers from The Cancer Genome Atlas (TCGA), and constructing a multi-cancer tracing and diagnostic model achieving 95.7% accuracy. TiSMeD serves as a robust, user-friendly platform integrating multi-omics data to advance epigenetic research and biomarker translation.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic Atlas of Bladder Cancer Reveals Master Transcription Factors and Risk-Associated Regulatory Elements in Luminal and Basal-Squamous Molecular Subtypes. Adib E, Nassar AH, Abou Alaiwi S, Baca SC, Hanlon T, Bou Farhat E, Tang Y, Corona RI, Seo JH, El Zarif T, Fonseca MAS, Acosta AM, Losko M, Zhang Z, Hirsch MS, Gusev A, Lawrenson K, Mouw KW, Choueiri TK, Kwiatkowski DJ, Freedman ML
Mol Cancer Res (Jun 2026)

We generated 64 epigenomic datasets using chromatin immunoprecipitation with sequencing and assay for transposase-accessible chromatin sequencing profiling on 28 fresh bladder cancer specimens of luminal and basal-squamous expression subtypes. An integrated analysis of core regulatory circuitry, enhancer activity, and transcription factor (TF) expression specificity nominated 23 luminal-specific and 14 basal-squamous-specific candidate master TFs (MTF), including established regulators like FOXA1, PPARG, and GATA3 for luminal bladder cancer and TP63 for basal-squamous bladder cancer, as well as new basal-squamous MTF candidates, SNAI2 and CEBPB. GRHL2, a regulator of subtype differentiation, was identified as a common MTF to luminal and basal-squamous bladder cancers. Cis-regulatory elements were enriched up to 80-fold for bladder cancer risk variants. Keratinization pathways were enriched in genetically determined basal-squamous sites, whereas carcinogen glucuronidation pathways were enriched in luminal sites. Integrating germline variation and epigenomics through a cistrome-wide association study identified a new bladder cancer risk locus upstream of SPINK1 and linked 10 of 19 bladder cancer risk loci to regulatory elements from a 350,000-sample genome-wide association study.]]> Wed, 31 Dec 1969 19:00:00 EST Arsenic exposure at birth, socioeconomic status, and epigenetic aging among adults in northern Chile. Kwon D, Bozack AK, Ferreccio C, McCormick N, Steinmaus CM, de la Rosa R, Cardenas A
Environ Res (Jun 2026)

Arsenic exposure remains a major global health concern, and early-life exposure has been linked to cancer, cardiovascular disease, and diabetes. Epigenetic biomarkers of aging may capture long-term effects of arsenic, yet whether exposure during sensitive developmental windows leaves detectable epigenetic signatures decades later remains unclear. Socioeconomic status (SES) may modify these relationships, yet its role as a modifier has not been examined.]]> Wed, 31 Dec 1969 19:00:00 EST Advances in Visualizing Cytosine Methylation and Allele-Specific Epigenetic States in Tissue Context. Kitazawa S, Haraguchi R, Kitazawa R
Pathol Int (Jun 2026)

Epigenetic regulation represents a heritable, sequence-independent layer of transcriptional control that critically shapes tissue morphology throughout development, homeostasis, and disease. Although immunohistochemical detection of histone modifications is now well established in diagnostic pathology, direct visualization of DNA methylation-the central mechanism underlying transcriptional silencing, genomic imprinting, and cellular identity-remains far more challenging. To address this limitation, a range of histochemical and cytochemical approaches has been developed to detect methylated cytosines within morphologically preserved tissues. Early strategies based on differential restriction enzyme sensitivity enabled global in situ assessment of CpG methylation, while bisulfite-dependent padlock-probe hybridization introduced sequence specificity through conversion-based discrimination of methylated and unmethylated cytosines. More recently, the ICON method has provided bisulfite-free, base-resolved detection of methylated CpG sites with single-cell precision, allowing direct visualization of allele-specific DNA methylation (ASM) within intact nuclei. These techniques reveal dynamic shifts between monoallelic and biallelic methylation during differentiation, exemplified by transitions at the Rankl promoter in osteogenic lineages. This review summarizes methodological advances in tissue-based DNA methylation detection and highlights how spatially resolved, sequence-specific approaches deepen our understanding of epigenetic regulation within histological architecture.]]> Wed, 31 Dec 1969 19:00:00 EST Charting the human-specific properties of gene expression networks in the infant prefrontal cortex. Klavert J, Radjabzadeh D, Gonzalez Sanchez E, Castelijns B, Timpanaro IS, Boers J, Fabro F, Vroeg In de Wei G, Bindels E, Kondova I, Gribnau J, Creyghton MP
Sci Adv (Jun 2026)

Human infancy is characterized by protracted brain development coinciding with sensitive periods of extensive synaptic remodeling. Whether this is supported by human infant-specific transcriptional programs is unknown as comparative material in closely related primate species was unavailable. Here, we analyze rare newborn chimpanzee and age-matched human and rhesus macaque brain samples using single-cell transcriptomics and epigenomics. We identify a human infant-specific transcriptional program in immature oligodendrocytes that is overrepresented in autism risk genes and patient gene expression changes. Furthermore, a human infant-specific transcriptional program in the neural lineage is overrepresented in Parkinson's disease risk genes and patient gene expression changes. Both of these programs are part of a core transcriptional network that contains human-specific sequence changes in regulatory DNA and lacks cell lineage specificity. Our study provides insights into the stage-specific properties of human evolution during early infancy and sheds light on the human-specific propensities to neural disease.]]> Wed, 31 Dec 1969 19:00:00 EST TomOmics: An integrative multi-omics platform for comparative and functional research in tomato. Wang Y, Yang T, Song Y, Yang Q, Su X, Li H, Li Y, Zhou M, Lin T
Mol Plant (Jun 2026)

Tomato (Solanum lycopersicum) is one of the world's most important vegetable crops and a model species for research within the Solanaceae family, holding both economic and scientific significance. Rapid progress in multi-omics technologies has transformed tomato research, generating large amounts of multi-omics data that require an efficient platform for integrated management and analysis. However, existing databases face challenges in effectively identifying genes of interest and supporting comparative studies across diverse cultivars and germplasm resources. To address these limitations, we developed the Tomato Multi-Omics Platform (TomOmics, http://tomatogenetics.cau.edu.cn), a comprehensive resource that integrates a wealth of multi-omics datasets, including genomics, variomics, transcriptomics, epigenomics, phenomics, and metabolomics from tomato and its closely related species. This platform encompasses multiple reference genomes, millions of annotated genes supported by diverse functional databases, extensive transcriptome data spanning multiple tissues and developmental stages, DNA methylation signals, as well as substantial genetic variants and metabolites. Leveraging these integrated resources, TomOmics was established as a comprehensive platform for pan-genome, comparative genomics, and transcriptome analysis specifically tailored to tomato research. Furthermore, it provides a multi-omics integration interface and a suite of user-friendly tools designed to support a wide range of customized bioinformatic analyses. TomOmics will serve as a valuable resource for advancing functional genomics studies and facilitating genetic breeding in tomato.]]> Wed, 31 Dec 1969 19:00:00 EST