'; ?> 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 Tue, 18 Mar 2025 20:32:25 EDT Tue, 18 Mar 2025 20:32:25 EDT jirtle@radonc.duke.edu james001@jirtle.com Applications of carbon dot-mediated transformation in plant (epi)genomic studies. She L, Cheng X, Tavakoli M, Borovskii G, Zhang W, Huang J
Trends Plant Sci (Mar 2025)

]]> Wed, 31 Dec 1969 19:00:00 EST FDPSM: Feature-Driven Prediction Modeling of Pathogenic Synonymous Mutations. Jin F, Cheng N, Wang L, Ye B, Xia J
J Chem Inf Model (Mar 2025)

Synonymous mutations, once considered to be biologically neutral, are now recognized to affect protein expression and function by altering the RNA splicing, stability, or translation efficiency. These effects can contribute to disease, making the prediction of the pathogenicity a crucial task. Computational methods have been developed to analyze the sequence features and biological functions of synonymous mutations, but existing methods face limitations, including scarcity of labeled data, reliance on other prediction tools, and insufficient representation of feature interrelationships. Here, we present FDPSM, a novel prediction method specifically designed to predict pathogenic synonymous mutations. FDPSM was trained on a robust data set of 4251 positive and negative training samples to enhance predictive accuracy. The method leveraged a comprehensive set of features, including genomic context, conservation, splicing effects, functional effects, and epigenomics, without relying on prediction scores from other mutation pathogenicity tools. Recognizing that original features alone may not fully capture the distinctions between pathogenic and benign synonymous mutations, we enhanced the feature set by extracting effective information from the interactions and distribution of these features. The experimental results showed that FDPSM significantly outperformed existing methods in predicting the pathogenicity of synonymous mutations, offering a more accurate and reliable tool for this important task. FDPSM is available at https://github.com/xialab-ahu/FDPSM.]]> Wed, 31 Dec 1969 19:00:00 EST Long non coding RNA function in epigenetic memory with a particular emphasis on genomic imprinting and X chromosome inactivation. Le LTT
Gene (Apr 2025)

Cells preserve and convey certain gene expression patterns to their progeny through the mechanism called epigenetic memory. Epigenetic memory, encoded by epigenetic markers and components, determines germline inheritance, genomic imprinting, and X chromosome inactivation. First discovered long non coding RNAs were implicated in genomic imprinting and X-inactivation and these two phenomena clearly demonstrate the role of lncRNAs in epigenetic memory regulation. Undoubtedly, lncRNAs are well-suited for regulating genes in close proximity at imprinted loci. Due to prolonged association with the transcription site, lncRNAs are able to guide chromatin modifiers to certain locations, thereby enabling accurate temporal and spatial regulation. Nevertheless, the current state of knowledge regarding lncRNA biology and imprinting processes is still in its nascent phase. Herein, we provide a synopsis of recent scientific advancements to enhance our comprehension of lncRNAs and their functions in epigenetic memory, with a particular emphasis on genomic imprinting and X chromosome inactivation, thus gaining a deeper understanding of the role of lncRNAs in epigenetic regulatory networks.]]> Wed, 31 Dec 1969 19:00:00 EST NONO interacts with nuclear PKM2 and directs histone H3 phosphorylation to promote triple-negative breast cancer metastasis. Li Q, Ci H, Zhao P, Yang D, Zou Y, Chen P, Wu D, Shangguan W, Li W, Meng X, Xing M, Chen Y, Zhang M, Chen B, Kong L, Zen K, Huang DCS, Jiang ZW, Zhao Q
J Exp Clin Cancer Res (Mar 2025)

Emerging evidence has revealed that PKM2 has oncogenic functions independent of its canonical pyruvate kinase activity, serving as a protein kinase that regulates gene expression. However, the mechanism by which PKM2, as a histone kinase, regulates the transcription of genes involved in triple-negative breast cancer (TNBC) metastasis remains poorly understood.]]> Wed, 31 Dec 1969 19:00:00 EST Reframing Formalin: A Molecular Opportunity Enabling Historical Epigenomics and Retrospective Gene Expression Studies. Holleley CE, Hahn EE
Mol Ecol Resour (Apr 2025)

Formalin preservation of museum specimens has long been considered a barrier to molecular research due to extensive crosslinking and chemical modification. However, recent optimisation of hot alkaline lysis and proteinase K digestion DNA extraction methods have enabled a growing number of studies to overcome these challenges and conduct genome-wide re-sequencing and targeted locus-specific sequencing. The newest, and perhaps most unexpected utility of formalin preservation in archival samples is its ability to preserve in situ DNA-protein interactions at a molecular level. Retrieving this signal provides information about the relative compaction or accessibility of the genome to the transcriptional machinery required for gene expression. Thus, exposure to formalin essentially corresponds to taking a snapshot of organism-wide gene expression at the time of death. While DNA methylation and RNA-Seq analyses of dried tissues have provided glimpses into historical gene regulation, these techniques were previously limited to skeletal or desiccated remains, offering only partial insights. By examining fluid-preserved specimens, molecular tools can now be applied to a broader range of tissues, enabling more detailed tissue-specific gene regulation profiling across vertebrates. In this review, we chronicle the historical use of formaldehyde in collections and discuss how targeted chromatin profiling with assays like MNase-seq and FAIRE-seq are surmounting fixation challenges and unlocking invaluable insights into historical genomes and gene expression profiles. The deeper integration of molecular genetics with museum collections bridges the gap between past and present and provides a vital tool that could help us predict and mitigate some of the impacts of future environmental change, novel pathogens, or invasive species.]]> Wed, 31 Dec 1969 19:00:00 EST Endothelial transcriptomic, epigenomic and proteomic data challenge the proposed role for TSAd in vascular permeability. Brash JT, Diez-Pinel G, Rinaldi L, Castellan RFP, Fantin A, Ruhrberg C
Angiogenesis (Mar 2025)

The vascular endothelial growth factor VEGF drives excessive vascular permeability to cause tissue-damaging oedema in neovascular and inflammatory diseases across multiple organs. Several molecular pathways have been implicated in VEGF-induced hyperpermeability, including binding of the VEGF-activated tyrosine kinase receptor VEGFR2 by the T-cell specific adaptor (TSAd) to recruit a SRC family kinase to induce junction opening between vascular endothelial cells (ECs). Inconsistent with a universal role for TSAd in permeability signalling, immunostaining approaches previously reported TSAd only in dermal and kidney vasculature. To address this discrepancy, we have mined publicly available omics data for expression of TSAd and other permeability-relevant signal transducers in multiple organs affected by VEGF-induced vascular permeability. Unexpectedly, TSAd transcripts were largely absent from EC single cell RNAseq data, whereas transcripts for other permeability-relevant signal transducers were detected readily. TSAd transcripts were also lacking from half of the EC bulk RNAseq datasets examined, and in the remaining datasets appeared at low levels concordant with models of leaky transcription. Epigenomic EC data located the TSAd promoter to closed chromatin in ECs, and mass spectrometry-derived EC proteomes typically lacked TSAd. By suggesting that TSAd is not actively expressed in ECs, our findings imply that TSAd is likely not critical for linking VEGFR2 to downstream signal transducers for EC junction opening.]]> Wed, 31 Dec 1969 19:00:00 EST Rare Causes and Differential Diagnosis in Patients With Silver-Russell Syndrome. Braga BL, da Cunha Scalco R, Homma TK, Freire BL, Cellin LP, Canton APM, Lerario AM, de Assis Funari MF, de Souza V, Bertola DR, Malaquias AC, Mendonca BB, de Lima Jorge AA
Clin Genet (Apr 2025)

Silver-Russell syndrome (SRS) is an imprinting disorder mainly characterized by pre- and postnatal growth restriction. Most SRS cases are due to 11p15.5 loss of methylation (11p15.5 LOM) or maternal uniparental disomy of chromosome 7 [UPD(7)mat], but several patients remain molecularly undiagnosed. This study describes the molecular investigation of children with a clinical diagnosis or suspicion of SRS at a tertiary center specialized in growth disorders. Thirty-nine patients were evaluated with multiplex ligation-dependent probe amplification, chromosomal microarray and/or massively parallel sequencing. The most common result was 11p15.5 LOM (n = 17; 43.5%), followed by UPD(7)mat (n = 2; 5.1%). Additionally, we found maternal duplications of the imprinting centers in 11p15.5 (n = 2; 5.1%), and genetic defects in SRS-causing genes (IGF2 and HMGA2) (n = 3; 7.7%; two mutations and one deletion). Alternative molecular diagnoses included UPD(14)mat (n = 1; 2,6%), UPD(20)mat (n = 1;2,6%), copy number variants (n = 2; 5.1%), and mutations in genes associated with other growth disorders (n = 4; 10.3%), leading to diagnoses of Temple syndrome, Mulchandani-Bhoj-Conlin syndrome, IGF-1 resistance (IGF1R), Bloom syndrome (BLM), Gabriele-De Vries syndrome (YY1), Intellectual developmental disorder autosomal dominant 50 with behavioral abnormalities (NAA15), and Intellectual developmental disorder 64 (ZNF292). These findings underscore the importance of establishing the molecular diagnosis of SRS and its differential diagnoses to guide appropriate management and genetic counseling.]]> Wed, 31 Dec 1969 19:00:00 EST Tracking and mitigating imprint erasure during induction of naive human pluripotency at single-cell resolution. Fischer LA, Meyer B, Reyes M, Zemke JE, Harrison JK, Park KM, Wang T, Jüppner H, Dietmann S, Theunissen TW
Stem Cell Reports (Mar 2025)

Naive human pluripotent stem cells (hPSCs) model the pre-implantation epiblast. However, parent-specific epigenetic marks (imprints) are eroded in naive hPSCs, which represents an important deviation from the epiblast in vivo. To track the dynamics of imprint erasure during naive resetting in real time, we established a dual-colored fluorescent reporter at both alleles of the imprinted SNRPN locus. During primed-to-naive resetting, SNRPN expression becomes biallelic in most naive cells, and biallelic SNRPN expression is irreversible upon re-priming. We utilized this live-cell reporter to evaluate chemical and genetic strategies to minimize imprint erasure. Decreasing the level of MEK/ERK inhibition or overexpressing the KRAB zinc-finger protein ZFP57 protected a subset of imprints during naive resetting. Combining these two strategies protected imprint levels to a further extent than either strategy alone. This study offers an experimental tool to track and enhance imprint stability during transitions between human pluripotent states in vitro.]]> Wed, 31 Dec 1969 19:00:00 EST Unraveling the intricate molecular landscape and potential biomarkers in lung adenocarcinoma through integrative epigenomic and transcriptomic profiling. Mukherjee A, Boonbangyang M, K S M
Sci Rep (Mar 2025)

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortalities, characterized by substantial genetic heterogeneity that challenges a comprehensive understanding of its progression. This study employs next-generation sequencing data analysis to transform our comprehension of LUAD pathogenesis. Integrating epigenetic and transcriptomic data of LUAD patients, this approach assessed the critical regulatory occurrences, identified therapeutic targets, and offered profound insights into cancer molecular foundations. We employed the DNA methylation data to identify differentially methylated CpG sites and explored the transcriptome profiles of their adjacent genes. An intersectional analysis of gene expression profiles uncovered 419 differentially expressed genes (DEGs) influenced by smoke-induced differential DNA methylation, among which hub genes, including mitochondrial ribosomal proteins (MRPs), and ribosomal proteins (RPs) such as MRPS15, MRPS5, MRPL33, RPL24, RPL7L1, MRPL15, TUFM, MRPL22, and RSL1D1, were identified using a network-based approach. These hub genes were overexpressed and enriched to RNA processing, ribosome biogenesis, and mitochondrial translation, which is critical in LUAD progression. Enhancer Linking Methylation/Expression Relationship (ELMER) analysis revealed transcription factor (TF) binding motifs, such as JUN, NKX23, FOSB, RUNX3, and FOSL1, which regulated these hub genes through methylation-dependent enhancer dynamics. Predominant hypomethylation of MRPs and RPs disrupted mitochondrial function, contributed to oxidative phosphorylation (OXPHOS) and metabolic reprogramming, favoring cancer cell survival. The survival analysis validated the clinical relevance of these hub genes, with high-expression cohorts exhibiting poor overall survival (OS) outcomes enlightened their relevance in LUAD pathogenesis and presented the potential for developing novel targeted therapeutic strategies.]]> 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 Semi-automated IT-scATAC-seq profiles cell-specific chromatin accessibility in differentiation and peripheral blood populations. Jin W, Ma J, Rong L, Huang S, Li T, Jin G, Zhou Z
Nat Commun (Mar 2025)

Single-cell ATAC-seq (scATAC-seq) enables high-resolution mapping of chromatin accessibility but is often limited by throughput, cost, and equipment requirements. Here, we present indexed Tn5 tagmentation-based scATAC-seq (IT-scATAC-seq), a semi-automated, cost-effective, and scalable approach that leverages indexed Tn5 transposomes and a three-round barcoding strategy. This workflow prepares libraries for up to 10,000 cells in a single day, reduces the per-cell cost to approximately $0.01, and maintains high data quality. Comprehensive benchmarking demonstrates that IT-scATAC-seq achieves robust library complexity, high signal specificity, and improved cost-efficiency compared to existing methods. We apply IT-scATAC-seq to mouse embryonic stem cells, capturing chromatin remodelling during early differentiation, and to human peripheral blood mononuclear cells, resolving cell-type-specific regulatory programs. Here, we show that IT-scATAC-seq provides a robust and efficient approach for high-resolution single-cell epigenomic investigations, balancing scalability, data quality, and accessibility.]]> Wed, 31 Dec 1969 19:00:00 EST Advances in molecular epidemiology of diabetic retinopathy: from genomics to gut microbiomics. Huang Y, Rao S, Sun X, Liu J
Mol Biol Rep (Mar 2025)

Diabetic retinopathy (DR) remains a prevalent complication of diabetes mellitus and a leading cause of blindness worldwide. The growing global diabetic population underscores the urgency to deepen our understanding of DR pathogenesis and develop effective prevention strategies. This review synthesizes recent advancements in molecular epidemiology, spanning genomics, epigenomics, transcriptomics, proteomics, metabolomics, and gut microbiomics, elucidating genetic underpinnings, epigenetic modifications, transcriptional alterations, protein biomarkers, metabolic disruptions, and gut microbiota dysbiosis associated with DR. Highlighted are key findings from genome-wide association studies (GWAS), Mendelian randomization (MR) studies, candidate gene association studies, and advancements in epigenetic mechanisms, revealing intricate disease pathways and potential therapeutic targets. Additionally, insights into altered metabolic profiles and gut microbiota compositions in DR underscore their emerging roles in disease progression and complications. Challenges and future directions in molecular epidemiological research are discussed to accelerate the translation of these findings into clinical applications for personalized DR management. The integration of multi-omics research findings may provide novel perspectives for facilitating rapid and accurate disease diagnosis, enabling dynamic disease monitoring, and advancing targeted therapeutic strategies.]]> Wed, 31 Dec 1969 19:00:00 EST Distinguishing Genetic Alterations Versus (Epi)Mutations in Silver-Russell Syndrome and Focus on the IGF1R Gene. Vimercati A, Tannorella P, Guzzetti S, Calzari L, Gentilini D, Manfredini E, Gori G, Gaudino R, Antona V, Piccione M, Daolio C, Auricchio R, Sirchia F, Minelli A, Rossi E, Bellini M, Biasucci G, Raucci AR, Pozzobon G, Patti G, Napoli F, Larizza L, Maghnie M, Russo S
J Clin Endocrinol Metab (Mar 2025)

Silver-Russell Syndrome (SRS) is a growth retardation disorder characterized by pre- and postnatal growth failure, relative macrocephaly at birth, prominent forehead, body asymmetry, and feeding difficulties. The main molecular mechanisms are imprinting alterations at multiple loci, though a small number of pathogenic variants have been reported in the SRS genes IGF2-PLAG1-HMGA2 and CDKN1C. However, around 40% of clinically suspected SRS cases do not achieve a molecular diagnosis, highlighting the necessity to uncover the underlying mechanism in unsolved cases.]]> Wed, 31 Dec 1969 19:00:00 EST Phosphatase PHLPP1 is an alveolar-macrophage-intrinsic transcriptional checkpoint controlling pulmonary fibrosis. Jiang Y, Zhang Y, Wang X, Xiang Y, Wang Z, Wang B, Ding Y, Gao Y, Rui B, Bai J, Ding Y, Chen C, Zhan Z, Liu X
Cell Rep (Mar 2025)

Alveolar macrophages (AMs) are crucial for lung homeostasis, and their dysfunction causes uncontrolled fibrotic responses and pulmonary disorders. Protein phosphatases control multiple cellular events. However, whether nuclear phosphatases cooperate with histone modifiers to affect pulmonary fibrosis progress remains obscure. Here, we identified pleckstrin homology domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) as a key protective factor for pulmonary fibrosis. Transcriptomics and epigenomics data confirmed that PHLPP1 selectively targeted Kruppel-like factor 4 (KLF4) for transcriptional inhibition in AMs. Nuclear PHLPP1 directly bound and dephosphorylated histone deacetylase 8 (HDAC8) at serine 39, thereby enhancing its deacetylase enzyme activity and subsequently suppressing KLF4 expression via the decreased histone acetylation and chromatin accessibility. Thus, loss of PHLPP1 amplified KLF4-centric profibrotic transcriptional program in AMs, while intratracheal administration of Klf4-short hairpin RNA (shRNA) adeno-associated virus ameliorated lung fibrosis in PHLPP1-deficient mice. Our study implies that targeting decreased PHLPP1 in AMs might be a promising therapeutic strategy for pulmonary fibrosis.]]> Wed, 31 Dec 1969 19:00:00 EST Extensive epigenomic dysregulation is a hallmark of homologous recombination deficiency in triple-negative breast cancer. Chen Y, Salas LA, Marotti JD, Jenkins NP, Cheng C, Miller TW, Kettenbach AN, Christensen BC
Int J Cancer (Mar 2025)

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with substantial disease heterogeneity, limited treatment options, and dismal clinical outcomes. Some TNBCs display homologous recombination deficiency (HRD), a phenotype with elevated genomic burden and worse prognosis if left untreated but chemotherapeutic sensitivity. While the molecular landscape of TNBC is distinct from other breast cancer subtypes, the TNBC-specific link between HRD and epigenome-wide methylation has not been established. This study reports two independent cohorts of TNBC tumors (n = 32 and n = 58) with HRD and epigenomic landscapes measured by the Multiplex Ligation-dependent Probe Amplification assay and the Illumina MethylationEPIC arrays, respectively. Genome-wide copy number and methylation alterations were significantly higher in HRD (all p <.05). Methylation of genome-wide repeat element Alu and transcriptional regulatory regions were significantly lower in HRD (all p <.05). An age-adjusted epigenome-wide association study of the continuous HRD probability scores revealed significant loci (all FDR <0.05) that were depleted from the CpG-rich "island" regions often seen in gene promoters but enriched in the CpG-poor "open sea" regions localized to gene enhancers. The significant loci implicated well-known candidate genes involved in the epithelial-to-mesenchymal transition, Wnt signaling, and DNA damage response. Supervised machine learning of HRD with nucleotide-specific methylation as the input enabled clinically relevant tumor stratification. Taken together, this study provides novel biological and translational insights into HRD in TNBCs.]]> Wed, 31 Dec 1969 19:00:00 EST Atlas of imprinted and allele-specific DNA methylation in the human body. Rosenski J, Peretz A, Magenheim J, Loyfer N, Shemer R, Glaser B, Dor Y, Kaplan T
Nat Commun (Mar 2025)

Allele-specific DNA methylation reflects genetic variation and parentally-inherited changes, and is involved in gene regulation and pathologies. Yet, our knowledge of this phenomenon is largely limited to blood. Here we present a comprehensive atlas of allele-specific DNA methylation using deep whole-genome sequencing across 39 normal human cell types. We identified 325k regions, covering 6% of the genome and 11% of CpGs, that show a bimodal distribution of methylated and unmethylated molecules. In 34k of these regions, genetic variations at individual alleles segregate with methylation patterns, validating allele-specific methylation. We also identified 460 regions showing parental allele-specific methylation, the majority of which are novel, as well as 78 regions associated with known imprinted genes. Surprisingly, sequence-dependent and parental allele-dependent methylation is often restricted to specific cell types, revealing unappreciated variation of allele-specific methylation across the human body. Finally, we validate tissue-specific, maternal allele-specific methylation of CHD7, offering a potential mechanism for the paternal bias in the inheritance mode of CHARGE syndrome associated with this gene. The atlas provides a resource for studying allele-specific methylation and regulatory mechanisms underlying imprinted expression in specific human cell types.]]> Wed, 31 Dec 1969 19:00:00 EST Long read sequencing enhances pathogenic and novel variation discovery in patients with rare diseases. Sinha S, Rabea F, Ramaswamy S, Chekroun I, El Naofal M, Jain R, Alfalasi R, Halabi N, Yaslam S, Sheikh Hassani M, Shenbagam S, Taylor A, Uddin M, Almarri MA, Du Plessis S, Alsheikh-Ali A, Abou Tayoun A
Nat Commun (Mar 2025)

With ongoing improvements in the detection of complex genomic and epigenomic variations, long-read sequencing (LRS) technologies could serve as a unified platform for clinical genetic testing, particularly in rare disease settings, where nearly half of patients remain undiagnosed using existing technologies. Here, we report a simplified funnel-down filtration strategy aimed at enhancing the identification of small and large deleterious variants as well as abnormal episignature disease profiles from whole-genome LRS data. This approach detected all pathogenic single nucleotide, structural, and methylation variants in a positive control set (N = 76) including an independent sample set with known methylation profiles (N = 57). When applied to patients who previously had negative short-read testing (N = 51), additional diagnoses were uncovered in 10% of cases, including a methylation profile at the spinal muscular atrophy locus utilized for diagnosing this life-threatening, yet treatable, condition. Our study illustrates the utility of LRS in clinical genetic testing and the discovery of novel disease variation.]]> Wed, 31 Dec 1969 19:00:00 EST RNA Modification in Metabolism. Liu Y, Sun Z, Gui D, Zhao Y, Xu Y
MedComm (2020) (Mar 2025)

Epigenetic regulation in disease development has been witnessed within this decade. RNA methylation is the predominant form of epigenetic regulation, and the most prevalent modification in RNA is N6-methyladenosine (mA). Recently, RNA modification has emerged as a potential target for disease treatment. RNA modification is a posttranscriptional gene expression regulation that is involved in both physiological and pathological processes. Evidence suggests that mA methylation significantly affects RNA metabolism, and its abnormal changes have been observed in a variety of diseases. Metabolic diseases are a series of diseases caused by abnormal metabolic processes of the body, the common metabolic diseases include diabetes mellitus, obesity, and nonalcoholic fatty liver disease, etc.; although the pathogenesis of these diseases differs from each other to the current understanding, most recent studies suggested pivotal role mA in modulating these metabolic diseases, and mA-based drug development has been on the agenda. This paper reviewed recent understanding of RNA modification in metabolic diseases, hoping to provide systematic information for those in this area.]]> Wed, 31 Dec 1969 19:00:00 EST Programmable mRNA therapeutics for controlled epigenomic modulation of single and multiplexed gene expression in diverse diseases. O'Donnell CW, Farelli JD, Belaghzal H, Chen J, Beech L, Sullivan J, Morrison-Smith C, Siecinski S, Katz A, Mildrum S, Gurnani M, Dhanania P, Webb CR, Castello Coatti G, Rumale P, Costa DFG, Gibson MI, Wang YE, Newman JV, McCauley TG
Nat Commun (Mar 2025)

Pathogenic gene dysregulation can be attributed to chromatin state change that pre-transcriptionally regulates expression. Recent breakthroughs elucidating the rules governing this DNA control layer, an epigenetic code, unlock a modality in precision medicine to target gene dysregulation across myriad diseases. Here we present a modular platform to design programmable mRNA therapeutics, Epigenomic Controllers (EC), that control gene expression through directed epigenetic change. By leveraging natural mechanisms, ECs tune expression levels of one or multiple genes with durable effect of weeks-to-months in female mice following a single dose. We design and characterize ECs to multiple target genes and identify an EC that effectively inhibits the cancer- and inflammatory-disorder-associated multi-gene cluster CXCL1-8. With precision targeting of NF-kB signaling and identification of homologous murine surrogates, ECs significantly reduce neutrophil migration in vivo during acute lung inflammation in female mice. A platform approach to EC design for epigenomic modulation expands treatment frontiers for diverse gene targets, including those considered "undruggable."]]> Wed, 31 Dec 1969 19:00:00 EST Application of Spatial Omics in the Cardiovascular System. Hu Y, Jia H, Cui H, Song J
Research (Wash D C) (2025)

Cardiovascular diseases constitute a marked threat to global health, and the emergence of spatial omics technologies has revolutionized cardiovascular research. This review explores the application of spatial omics, including spatial transcriptomics, spatial proteomics, spatial metabolomics, spatial genomics, and spatial epigenomics, providing more insight into the molecular and cellular foundations of cardiovascular disease and highlighting the critical contributions of spatial omics to cardiovascular science, and discusses future prospects, including technological advancements, integration of multi-omics, and clinical applications. These developments should contribute to the understanding of cardiovascular diseases and guide the progress of precision medicine, targeted therapies, and personalized treatments.]]> Wed, 31 Dec 1969 19:00:00 EST