'; ?> 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 Mon, 09 Mar 2026 07:02:57 EDT Mon, 09 Mar 2026 07:02:57 EDT jirtle@radonc.duke.edu james001@jirtle.com OsCLSY4 modulates epigenomic patterns and grain size in rice. Zhang R, Chen Y, Xu M, Zhang Y, Liu Y, Wang L, Liu JX, Hong L, Yang Y, Zhou M
Plant J (Mar 2026)

De novo DNA methylation, orchestrated by the RNA-directed DNA methylation (RdDM) pathway, is essential for gene regulation and transposon silencing. While CLASSY (CLSY) proteins facilitate RNA POLYMERASE IV (Pol IV) recruitment to initiate the RdDM pathway in plants, their roles in crops are incompletely explored. Here, we report OsCLSY4 as the dominant regulator within the OsCLSY family, driving Pol IV-mediated epigenomic patterns and influencing diverse agricultural traits. Epigenomics analyses reveal that OsCLSY4 controls over 95% of Pol IV-dependent 24-nucleotide small interfering RNA (24-nt siRNA) clusters and more than 70% of Pol IV-dependent hypomethylated CHH differentially methylated regions (DMRs), predominantly at miniature inverted-repeat transposable elements (MITEs). Loss of OsCLSY4 leads to dysregulation of MADS22 and GA20ox1 in a DNA methylation-dependent manner. SunTag-mediated targeted demethylation confirms that reduced DNA methylation in promoter regions leads to MADS22 activation and GA20ox1 repression to influence grain size, linking epigenetic changes to phenotypic outcomes of osclsy4. Moreover, OsCLSY4 governs tissue-specific methylation patterns in panicle and seedling. Mechanistically, OsCLSY4 is the predominantly expressed OsCLSY family member and interacts with Pol IV. Collectively, our findings position OsCLSY4 as a central hub for Pol IV-mediated epigenomic regulation in rice and suggest its potential utility in epigenetic breeding strategies.]]> Wed, 31 Dec 1969 19:00:00 EST Superenhancer-mediated ferroptosis in age-related hearing loss: cochlear epigenomics. Zhang C, Yang T, Luo X, Fu X, Sun Y, Yuan W
Cell Mol Life Sci (Mar 2026)

Age-related hearing loss (ARHL), also known as presbycusis, is a prevalent condition among older adults and affects a substantial proportion of the global aging population. The underlying mechanisms of ARHL remain unclear, and this study aimed to explore the role of superenhancers (SEs) and the transcription factor Sp1 in regulating hair cell (HC) aging and ferroptosis, a form of regulated cell death associated with iron metabolism.]]> 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 ‑folate axis as a modulator of the epigenetic landscape in autoimmune diseases (Review). Navarro-Rodríguez PM, Bajeca-Serrano RF, Turrubiates-Hernández FJ, Ceja-Gálvez HR, Hernández-Bello J, Hernández-Ramírez CO, Ramírez-de Los Santos S, Muñoz-Valle JF
Int J Mol Med (Mar 2026)

The one‑carbon metabolism pathway, regulated by the methylenetetrahydrofolate reductase (MTHFR) enzyme, represents a key nexus where genetic predisposition and nutrient status converge to shape the epigenetic landscape of autoimmune diseases. The objective of the present review is to synthesize evidence of how the ‑folate axis drives epigenomic patterns in these conditions. One of the main diseases involved is rheumatoid arthritis, where drug‑naïve patients show T‑cell and synovial hypomethylation with cytokine‑driven DNMT suppression, a process aggravated by reduced folate availability and polymorphisms that constrain S‑adenosylmethionine supply. Similarly, in systemic lupus erythematosus, CD4 T cells exhibit global hypomethylation with an interferon‑skewed signature (such as ), associated with impaired activity and a folate‑dependent SAM:SAH imbalance that further diminishes DNMT function. Finally, in celiac disease, intestinal differential methylation, including LINE‑1 hypomethylation, is observed, driven by gluten‑induced villous atrophy and folate malabsorption. Overall, impaired one‑carbon metabolism and ‑dependent methylation capacity may be key determinants of epigenomic dysfunction underlying autoimmune disease and its clinical severity.17.]]> Wed, 31 Dec 1969 19:00:00 EST Introduction to the special issue on epigenetic regulation of chronic pain. Nackley AG
Pain Rep (Apr 2026)

This Special Issue features 6 articles from leaders in the field that elucidate novel epigenetic mechanisms regulating nociception, inflammation, responses to pharmacologic and integrative therapies, and pain disparities among racial/ethnic groups. Together, they highlight the expanding potential of epigenomics to inform mechanistic discovery, guide personalized pain therapeutics, and advance pain equity.]]> Wed, 31 Dec 1969 19:00:00 EST Multi-omics biomarker detection in Diethylnitrosamine (DENA) induced hepatocellular carcinoma. Afzal O, Goud P, Goyal K, Altharawi A, Alamri MA, Alossaimi MA, Altamimi ASA, Pandey SN
Clin Chim Acta (Mar 2026)

Hepatocellular carcinoma (HCC) is frequently diagnosed at an advanced stage due to tumor heterogeneity and chronic liver damage, which reduce the performance of single biomarkers and complicate the clinical interpretation of laboratory results. The genotoxic diethylnitrosamine (DENA)-induced hepatocarcinogenesis model provides a stage-resolved and experimentally controlled framework associated with genotoxic stress, inflammation, and fibrosis, along with metabolic adaptation in target tissues and circulating biofluids. This review summarizes multi-omics data from DENA models and translational cohorts, encompassing genomics/epigenomics, transcriptomics, proteomics, metabolomics, and glycomics, as well as liquid biopsy analytes, including cell-free DNA, extracellular vesicle cargo, and circulating tumor cell markers. We integrated the dynamics of injury progression to fibrosis and tumor development at the pathway scale, highlighting multi-analyte biomarker sets that improve the differentiation between advanced fibrosis/cirrhosis and early hepatocellular carcinoma (HCC). Additionally, we examined enabling technologies in analytical techniques, including targeted mass spectrometry (MS), PCR-based methods, and clinically scalable glycoprofiling. Notably, we propose a stage-aware biomarker selection paradigm that emphasizes mechanistic consistency, analytical viability, and clinical actionability to facilitate earlier identification and longitudinal tracking. Finally, we discuss the practical implications of multicenter validation and a harmonized study design to enhance reproducibility and expedite clinical translation.]]> Wed, 31 Dec 1969 19:00:00 EST Rising Star: Single Cell Omics Technologies: When Whole Omics Analysis Meets Single Cell Resolution. Tang F
J Mol Biol (Apr 2026)

I got my PhD degree under the supervision of Prof. Kegang Shang in 2003. And I did my postdoc research in Azim Surani's lab. Then I set up my own lab in Biomedical Pioneering Innovation Center at Peking University in 2010. My research has focused on developing single-cell omics sequencing technologies and employing these powerful tools to dissect the gene regulation networks in human germline cell development under both physiological and pathological conditions. My lab systematically developed a serial of single-cell omics sequencing technologies, including the first single-cell DNA methylome sequencing technology in 2013, which was considered to pioneer the single-cell epigenome field. In recent years, my lab has focused on developing single-cell omics long-read sequencing technologies based on single-molecule sequencing platforms, which can reveal critical features of the repetitive elements. The repetitive elements are considered as 'dark matter', which account for over half of our genome and play important roles for both normal development and numerous diseases. The research in my lab revealed critical features of the epigenetic reprogramming of human germline cells, deepening our understanding of these cells, which are fundamental to the transgenerational immortality of the human species.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic Clocks of Biological Aging and Risk of Incident Mild Cognitive Impairment and Dementia: The Women's Health Initiative Memory Study. Nguyen S, Lu AT, Horvath S, Espeland MA, Rapp SR, Maihofer AX, Nievergelt CM, LaCroix AZ, McEvoy LK, Resnick SM, Beckman K, Shadyab AH
Aging Cell (Mar 2026)

Aging is the strongest risk factor for dementia; however, few studies have examined the association of biological aging with incident dementia. We analyzed 6069 cognitively unimpaired women (mean age = 70.0 ± 3.8 years) in the Women's Health Initiative Memory Study to examine the association of accelerated biological aging, measured with second and third-generation epigenetic clocks (AgeAccelPheno and AgeAccelGrim2, and DunedinPACE, respectively) with incident mild cognitive impairment (MCI) and probable dementia. Multivariable Cox proportional hazards models adjusted for age, education, race, ethnicity, smoking, hormone therapy regimen, physical activity, body mass index, and estimated white blood cell counts. For comparison, we also examined first-generation epigenetic clocks (AgeAccelHorvath; AgeAccelHannum). We evaluated effect modification by age, race/ethnicity, hormone therapy regimen, menopause type (natural vs. surgical), and APOE ε4 carriage. There were 1307 incident MCI or probable dementia events over a median follow-up of 9.3 (25th percentile = 6.1, 75th percentile = 16.1) years. The adjusted HRs (95% CI; p-value) for incident MCI/probable dementia per one-standard deviation increment were 1.07 (1.01-1.15; p = 0.03) for DunedinPACE, 1.11 (1.02-1.20; p = 0.01) for AgeAccelGrim2, and 1.01 (0.95-1.07; p = 0.74) for AgeAccelPheno. Only AgeAccelGrim2 remained significant under the Bonferroni-corrected threshold for significance (p < 0.02). Other epigenetic clocks were not associated with incident MCI/probable dementia. There was no effect modification in most subgroup analyses (p-interaction ≥ 0.05). In this cohort study of older women, accelerated biological aging measured by AgeAccelGrim2 was associated with higher risk of incident MCI/probable dementia. These findings provide evidence linking epigenetic biomarkers of biological aging with MCI and dementia development, independent of chronological age.]]> Wed, 31 Dec 1969 19:00:00 EST DNA methylation-mediated alterations in Copper(I/II) redox equilibrium underlie lead-induced neurotoxicity. Hu J, Wang WX
Environ Pollut (Apr 2026)

Lead (Pb), a ubiquitous environmental toxin, poses significant risks to central nervous system health, primarily by disrupting essential metal homeostasis in the brain. While epigenetic regulation and proteomic expression are significantly affected by Pb, its specific molecular impact on copper (Cu) redox states remains poorly understood. This study systematically investigated the molecular mechanisms underlying Pb-induced neurotoxicity in SH-SY5Y cells through integrated epigenomics and proteomics analysis. DNA methylation analysis revealed 141,357 differentially methylated regions (DMRs), primarily in CpG sites, with 62.6 % hypermethylated and 37.4 % hypomethylated. These DMRs were enriched in genes associated with critical processes such as metal ion binding, cell cycle regulation, and nervous system development. Promoter-specific methylation changes were notably pronounced, impacting pathways linked to neurodegenerative diseases, including Alzheimer's disease. Proteomic analysis identified 740 differentially expressed proteins (DEPs), with 366 upregulated and 374 downregulated in Pb-treated cells. Functional annotation revealed significant enrichment of DEPs in mitochondria, where Pb exposure disrupted processes related to oxidative phosphorylation, ion transport, and transmembrane processes. These proteomic changes aligned with the observed epigenetic modifications, reinforcing the role of Pb in impairing neuronal function via its effects on cellular energy metabolism and metal ion dynamics. Notably, Pb exposure disrupted Cu redox transitions between Cu(I) and Cu(II) as well as glutathione (GSH) activity, underscoring its impact on cellular metal homeostasis regulation and oxidative imbalance. In summary, this study provides a comprehensive view of how Pb exposure alters epigenetic and proteomic landscapes, disrupting key biological processes and pathways essential for neuronal health.]]> 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 : a computational suite for DNA methylation sequencing data analysis. Loyfer N, Rosenski J, Kaplan T
Life Sci Alliance (Apr 2026)

Next-generation methylation-aware sequencing of DNA sheds light on the fundamental role of methylation in cellular function in health and disease, increasing the number of covered CpG sites from hundreds of thousands in previous array-based approaches to tens of millions across the whole genome. While array-based approaches are limited to single-CpG resolution, next-generation sequencing allows for a more detailed, single-molecule fragment-level analysis; however, existing tools to fully use this capability are not yet well developed. Here, we present , an extensive computational suite tailored for methylation sequencing data. allows fast access and ultracompact anonymized representation of high-throughput methylome data, obtained through various library preparation and sequencing methods, with a custom epiread file format achieving a compression factor of over 100x from the input BAM file. In addition, contains state-of-the-art algorithms for genomic segmentation, biomarker identification, genetic and epigenetic data integration, and more. offers fragment-level analysis and informative visualizations, across multiple genomic regions and samples.]]> Wed, 31 Dec 1969 19:00:00 EST Integrative epigenomic landscape of Alzheimer's Disease brains reveals oligodendrocyte molecular perturbations associated with tau. Oatman SR, Reddy JS, Atashgaran A, Wang X, Min Y, Quicksall Z, Vanelderen F, Carrasquillo MM, Liu CC, Yamazaki Y, Nguyen TT, Heckman M, Zhao N, DeTure M, Murray ME, Bu G, Kanekiyo T, Dickson DW, Allen M, Ertekin-Taner N
Nat Commun (Mar 2026)

Alzheimer's disease (AD) brains have variable neuropathologic and biochemical changes. Capturing epigenetic factors associated with this variability can reveal novel biological insights into AD pathophysiology. Here, we conduct an epigenome-wide association study of DNA methylation in 472 AD brains with neuropathologic and biochemical brain protein levels core to AD pathogenesis. Using a novel regional methylation (rCpGm) approach, we identify 5478 significant associations, 99.7% of which associate with tau biochemical measures, and 93 concordant associations in external datasets. Transcriptome-methylome integration reveals enrichment in oligodendrocyte genes, including known AD risk gene BIN1, myelination genes MYRF, MBP and MAG previously implicated in AD, and novel genes like LDB3. Further characterization of these perturbations in independent AD and primary tauopathy datasets highlights consistent tau-related associations. In summary, we uncover the integrative epigenomic landscape of AD, demonstrate tau-related oligodendrocyte gene perturbations as a common potential pathomechanism across tauopathies and share findings via our Multiomic Atlas.]]> Wed, 31 Dec 1969 19:00:00 EST Synergistic integration of clinical and multi-omics data for early MCI diagnosis using an attention-based graph fusion network. Yu S, Zhao J, Ouyang J, Wang X, Kou P, Zhu K, Liu P
J Neurosci Methods (Apr 2026)

Mild cognitive impairment (MCI), a precursor to Alzheimer's disease (AD), requires precise early diagnosis. Single-omics approaches often miss disease complexity, motivating integrative and interpretable solutions.]]> Wed, 31 Dec 1969 19:00:00 EST The maternal-effect gene ZmGRP23 promotes PPR-DYW-mediated RNA editing in maize mitochondria. Yang YZ, Zhang SG, Chen YM, Ren YT, Gao S, Liu XY, Xu C, Tan BC
Plant Physiol (Mar 2026)

The maternal effect is a non-Mendelian inheritance phenomenon in which the maternal genotype regulates offspring traits via gametic cytoplasmic components or genomic imprinting. Hundreds of maternal-effect genes have been identified; however, the underlying molecular mechanisms and biological roles of these genes remain unclear. Here we report that ZmGRP23 is a maternal-effect gene that regulates maize (Zea mays) seed development by mediating mitochondrial RNA editing. The maize GLUTAMINE-RICH PROTEIN23 (GRP23) encodes an atypical pentatricopeptide repeat (PPR) protein with a unique C-terminal domain. ZmGRP23 exhibits maternal expression dominance in a genetic background-dependent manner (e.g., W22). Loss of ZmGRP23 function arrests zygotic development at very early stages and reduces pollen transmission. Low expression of ZmGRP23 reduces the RNA editing efficiency at 190 mitochondrial sites in the endosperm, and most of these sites depend on canonical PPR-DYW proteins for editing. ZmGRP23 shows no or weak interaction with the full length of canonical PPR-DYW proteins; however, it strongly interacts with the E and the carboxyl terminus of DYW domains of these proteins. PPR-DYW proteins strongly interact with maize multiple organellar RNA-editing factor1 (MORF1) and MORF8, both of which also bind ZmGRP23. ZmMORF enhances the interaction between ZmGRP23 and PPR-DYW proteins. This implies that ZmMORF binding may induce conformational changes in PPR-DYW proteins, exposing ZmGRP23 interaction interfaces and promoting ZmGRP23 recruitment. This study reveals that ZmGRP23 mediates mitochondrial RNA editing through non-canonical recruitment of canonical PPR-DYW proteins and implies that an epigenetic-mitochondrial regulatory axis bridges RNA editing plasticity to seed development.]]> Wed, 31 Dec 1969 19:00:00 EST Portrait of a Spectrum: Clinical and Genetic Characterization of a Large Cohort of Chromatinopathies-30 Years' Experience From a Third Level Center. Marchetti GB, Rosina E, Meossi C, Mura M, Pezzani L, Selicorni A, Bedeschi MF, Tenconi R, Agostoni C, Finelli P, De Matteis S, Di Fede E, Massa V, Pezzoli L, Gervasini C, Iascone M, Milani D
Clin Genet (Apr 2026)

Chromatinopathies (CPs) are an expanding group of rare genetic disorders affecting epigenetic machinery. Besides an intricate genotypic spectrum, these conditions share overlapping phenotypes characterized by neurocognitive impairment, growth defects and distinctive, but often convergent, facial features. Although individually rare, the landscape of CPs is increasingly growing and represents an emerging and possibly underestimated cause of disability. Due to their complexity and rarity, accurate diagnosis and management pose significant difficulties. To address these challenges and gain a deeper overview of these diseases' spectrum, we retrospectively collected clinical characteristics of 239 patients diagnosed with CPs and critically analyzed their diagnostic journey, growth charts, neurological and gestaltic features. Starting from the largest collection of CPs to date, our data point to wide sequencing analyses as the best shortcut to diagnosis. We have also demonstrated the importance of growth defects in this group of disorders that require dedicated growth tables, and we have delved into the great variability of neurological and clinical burden in these conditions. This retrospective study provides a significant advance in our understanding of these rare diseases and will help to improve diagnostic, therapeutic, and clinical approaches to CPs and to develop personalized multidisciplinary care plans for affected patients.]]> Wed, 31 Dec 1969 19:00:00 EST Multiomics approaches in Kawasaki disease: insights into pathogenesis and emerging directions for diagnosis and treatment. Ahn JG, Kang I
Clin Exp Pediatr (Mar 2026)

Kawasaki disease (KD) is an acute febrile vasculitis and the leading cause of acquired heart disease in children. Despite decades of research, the etiology remains unknown and key mechanisms linking systemic inflammation to coronary artery lesions are incompletely defined. High-throughput technologies-including genomics, transcriptomics, proteomics, metabolomics, epigenomics, and immunomics-have enabled systems-level profiling of KD and highlighted reproducible inflammatory and vascular pathways. Multiomics integration increasingly supports convergent mechanistic axes, particularly interleukin (IL-1/IL-6-neutrophil programs, Fcγ-receptor signaling related to intravenous immunoglobulin (IVIG) pharmacodynamics, Ca²+/nuclear factor of activated T cells-dependent T-cell activation, and endothelial/extracellular matrix remodeling associated with coronary outcomes. While these findings provide a robust framework for biomarker discovery and therapeutic hypothesis generation, most signatures remain investigational and require prospective validation, standardized sampling (pre-/post-IVIG), and clinically scalable assays before routine implementation. This review summarizes current multiomics applications in KD, prioritizes the most consistently supported pathways, and outlines a pragmatic roadmap toward clinically useful risk stratification, disease monitoring, and outcome prediction.]]> Wed, 31 Dec 1969 19:00:00 EST Multi-omics biomarker detection in smoking induced COPD. Syed RU, Khaled Bin Break M, Akasha R, Elafandy NM, Abobaker SH, Khalifa AAS, Aboshouk NAM, Nashmi Alghaythi A, Altwalah LA, Menwer Aldhafeeri RM, Khan MSA, Gupta G
Clin Chim Acta (Mar 2026)

Chronic obstructive pulmonary disease (COPD) is marked by heterogeneity, and traditional spirometric biomarkers fall short of fully capturing its underlying molecular complexity. This review discusses recent developments in multi-omics profiling, such as transcriptomics, proteomics, metabolomics, and epigenomics/acetylomics, to define biologically meaningful COPD endotypes and enhance their clinical categorization. Reproducible circulating protein markers identified in proteomic studies include surfactant protein D (SP-D), club cell secretory protein (CC16), fibrinogen, and inflammatory cytokines, which predict disease severity, risk of exacerbation, and mortality. Further evidence of dysregulated histone/protein acetylation and other post-translational modifications in chronic inflammation, steroid resistance, and disease progression is provided by epigenomic studies (such as DNA methylation, non-coding RNAs, and chromatin remodeling) and acetylomic analyses. Notably, integrative multi-omics solutions exhibit better outcomes than single-biomarker solutions by allowing the identification of molecular endotypes that are more likely to accommodate clinical heterogeneity. Nevertheless, it is significantly constrained by cohort and platform heterogeneity, including factors such as smoking exposure, age, comorbidities, treatment, and sample processing methods. Overall, the existing evidence highlights the importance of multi-omics integration in the further development of precision diagnostics and individualized management of COPD, bridging the gap between molecular pathology and clinical decision-making.]]> Wed, 31 Dec 1969 19:00:00 EST Single-Cell Multimodal Profiling Highlights Persistent Aortic Smooth Muscle Cell Changes in Diabetic Mice Despite Glycemic Control. Tanwar VS, Malek V, Wang J, Luo Y, Malhi NK, Zhang H, Abdollahi M, Lanting L, Senapati P, Das S, Reddy MA, Zang C, Miller CL, Chen ZB, Natarajan R
Arterioscler Thromb Vasc Biol (Mar 2026)

Type 2 diabetes is associated with accelerated vascular complications such as hypertension and atherosclerosis. Phenotypic switching of vascular smooth muscle cells (SMCs), a major driver of these complications, is enhanced in diabetes. Despite adequate glycemic control, SMC dysfunction can persist due to metabolic memory of prior hyperglycemia. However, the mechanisms are unclear. Here, leveraging single-cell multiomics, we examined the effect of glucose normalization on transcriptomic and epigenomic changes associated with SMC phenotypic transition in type 2 diabetes mice.]]> Wed, 31 Dec 1969 19:00:00 EST Dissecting spatial patterning and signaling with directional diffusion in spatial multi-omics. Wang H, Yuan Z, Su Y, Zheng C, Sun X
Proc Natl Acad Sci U S A (Mar 2026)

Spatial multi-omics sequencing enables the simultaneous profiling of transcriptomics, proteomics, and epigenomics at a spatial resolution, offering insights into complex tissue organization and molecular regulation. However, the effective integration of multiple omics modalities in a spatial context remains a major challenge. Here, we present SpaDDM, a spatial multi-omics integration framework based on directional diffusion models (DDMs), which supports spatial pattern identification, cross-omics alignment, and inter-and intracellular signaling flow analysis. SpaDDM employs DDM-based graph networks to learn omics-specific representations by jointly incorporating spatial coordinates and molecular measurements within each modality, followed by an attention mechanism to align features across modalities. We benchmarked SpaDDM on diverse spatial multi-omics datasets, including transcriptomics-epigenomics and transcriptomics-proteomics combinations across multiple tissues and species. SpaDDM consistently outperformed existing methods by more accurately deciphering spatial tissue patterns and effectively reducing the boundary noise between spatial regions. Moreover, the learned low-dimensional coembedded representations of individual cells serve as integral mediators for inferring the signaling flows that underlie spatial patterning. Finally, we demonstrated that SpaDDM alignment of complementary information across multi-omics layers facilitates cross-omics translation and significantly improves the prediction of cell state alignments.]]> Wed, 31 Dec 1969 19:00:00 EST Computational methods for spatial multi-omics integration. Geng A, Cui C, Luo Z, Xu J, Meng Y, Cui F, Wei L, Zou Q, Zhang Z
Biotechnol Adv (2026)

The rapid development of spatial multi-omics technologies has enabled the simultaneous acquisition of transcriptomic, proteomic, and epigenomic information from the same tissue section. However, substantial differences in distributional properties, data dimensionality, and noise levels across modalities, together with the inherent sparsity and incompleteness of spatial information, pose major challenges for data integration and modeling. In recent years, deep learning-based spatial multi-omics integration algorithms have emerged rapidly, offering new approaches for constructing unified latent representations and achieving cross-modal fusion. In this review, we systematically summarize existing spatial multi-omics integration methods for the first time, categorizing and comparing them from two perspectives. We not only systematically surveyed the datasets employed by these methods, but also highlighted the key downstream analytical tasks they support, and further summarized the major challenges currently faced in spatial multi-omics integration research. Furthermore, we compare the strengths and limitations of different approaches to assist researchers in selecting appropriate methods more efficiently, thereby advancing the application of spatial multi-omics in uncovering multilayer regulatory mechanisms of tissue microenvironments and disease processes.]]> Wed, 31 Dec 1969 19:00:00 EST