'; ?> 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, 31 Mar 2025 22:00:24 EDT Mon, 31 Mar 2025 22:00:24 EDT jirtle@radonc.duke.edu james001@jirtle.com A combination of transcriptomics and epigenomics identifies genes and regulatory elements involved in embryonic tail development in the mouse. Chen YX, Zhang XP, Cooper DN, Wu DD, Bao WD
BMC Biol (Mar 2025)

The post-anal tail is a common physical feature of vertebrates including mammals. Although it exhibits rich phenotypic diversity, its development has been evolutionarily conserved as early as the embryonic period. Genes participating in embryonic tail morphogenesis have hitherto been widely explored on the basis of experimental discovery, whereas the associated cis-regulatory elements (CREs) have not yet been systematically investigated for vertebrate/mammalian tail development.]]> Wed, 31 Dec 1969 19:00:00 EST Chromatin accessibility landscape of mouse early embryos revealed by single-cell NanoATAC-seq2. Li M, Jiang Z, Xu X, Wu X, Liu Y, Chen K, Liao Y, Li W, Wang X, Guo Y, Zhang B, Wen L, Kee K, Tang F
Science (Mar 2025)

In mammals, fertilized eggs undergo genome-wide epigenetic reprogramming to generate the organism. However, our understanding of epigenetic dynamics during preimplantation development at single-cell resolution remains incomplete. Here, we developed scNanoATAC-seq2, a single-cell assay for transposase-accessible chromatin using long-read sequencing for scarce samples. We present a detailed chromatin accessibility landscape of mouse preimplantation development, revealing distinct chromatin signatures in the epiblast, primitive endoderm, and trophectoderm during lineage segregation. Differences between zygotes and two-cell embryos highlight reprogramming in chromatin accessibility during the maternal-to-zygotic transition. Single-cell long-read sequencing enables in-depth analysis of chromatin accessibility in noncanonical imprinting, imprinted X chromosome inactivation, and low-mappability genomic regions, such as repetitive elements and paralogs. Our data provide insights into chromatin dynamics during mammalian preimplantation development and lineage differentiation.]]> 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 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 Parent-of-Origin Effects in Childhood Asthma at Seven Years of Age. Lee Y, Gjerdevik M, Jugessur A, Gjessing HK, Corfield E, Havdahl A, Harris JR, Magnus MC, HÃ¥berg SE, Magnus P
Genet Epidemiol (Apr 2025)

Childhood asthma is more common among children whose mothers have asthma than among those whose fathers have asthma. The reasons for this are unknown, and we hypothesize that genomic imprinting may partly explain this observation. Our aim is to assess parent-of-origin (PoO) effects on childhood asthma by analyzing SNP array genotype data from a large population-based cohort. To estimate PoO effects in parent-reported childhood asthma at 7 years of age, we fit a log-linear model implemented in the HAPLIN R package to SNP array genotype data from 915 mother-father-child case triads, 603 mother-child case dyads, and 113 father-child case dyads participating in the Norwegian Mother, Father, and Child Cohort Study (MoBa). We found that alleles at two SNPs-rs3003214 and rs3003211-near the adenylosuccinate synthase 2 gene (ADSS2 on chromosome 1q44) showed significant PoO effects at a false positive rate ≤ 0.05. The ratio of the effect of the maternally and paternally inherited G-allele at rs3003214 was 1.68 (95% CI: 1.41-2.03, p value = 1.13E-08). Our results suggest PoO effects at the ADSS2 gene, particularly the maternally inherited G-allele at rs3003214, may contribute to the maternal effect in childhood asthma.]]> Wed, 31 Dec 1969 19:00:00 EST Progress on Multiomics Research on Acne Vulgaris: A Literature Review. Lai Y, Fan M, Fan X, Chen J, Xiang LF, Ma Y
J Invest Dermatol (Mar 2025)

Acne vulgaris, a prevalent chronic inflammatory disease of the pilosebaceous unit, continues to present with a complex pathogenesis that is not fully understood. The advent of high-throughput sequencing technologies has revolutionized biomedical research, enabling the comprehensive use of multiomics analyses to study diseases with intricate mechanisms, such as acne. This review summarizes the progress in genomics, epigenomics, transcriptomics, proteomics, and metabolomics research on acne. By providing a comprehensive overview, we aim to enhance our understanding of acne pathogenesis and identify potential therapeutic targets that could inspire the prevention and treatment of acne.]]> Wed, 31 Dec 1969 19:00:00 EST Modified carbon dot-mediated transient transformation for genomic and epigenomic studies in wheat. She L, Cheng X, Jiang P, Shen S, Dai F, Run Y, Zhu M, Tavakoli M, Yang X, Wang XE, Xiao J, Chen C, Kang Z, Huang J, Zhang W
Plant Biotechnol J (Apr 2025)

Genotype restriction poses a significant bottleneck to stable transformation in the vast majority of plant species, thereby severely impeding advancement in plant bioengineering, particularly for crops. Nanoparticles (NPs) can serve as effective carriers for the transient delivery of nucleic acids, facilitating gene overexpression or silencing in plants in a genotype-independent manner. However, the applications of NP-mediated transient systems in comprehensive genomic studies remained underexplored in plants, especially in crops that face challenges in genetic transformation. Consequently, there is an urgent need for efficient NP-mediated delivery systems capable of generating whole plants or seedlings with uniformly transformed nucleic acids. We have developed a straightforward and efficient modified carbon dot (MCD)-mediated transient transformation system for delivering DNA plasmids into the seeds of wheat, which is also applicable to other plant species. This system facilitates the generation of whole seedlings that contain the transferred DNA plasmids. Furthermore, our study demonstrates that this system serves as an excellent platform for conducting functional genomic studies in wheat, including the validation of gene functions, protein interactions and regulation, omics studies, and genome editing. This advancement significantly enhances functional genomic research for any plants or crops that face challenges in stable transformation. Thus, our study provides for the first time evidence of new applications for MCDs in functional genomics and epigenomic studies, and bioengineering potentially leading to the improvement of desirable agronomic traits in crops.]]> 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 GWAS for Defining the Pathogenesis of Hypertension: Have They Delivered? Alexander MR, Edwards TL, Harrison DG
Hypertension (Apr 2025)

Genome-wide association studies have identified >3500 associated single nucleotide polymorphisms and over 1000 independent loci associated with hypertension. These individually have small effect sizes, and few associated loci have been experimentally tested for causal roles in hypertension using animal models or in humans. Thus, methods to prioritize and maximize the relevance of identified single nucleotide polymorphisms and associated loci are critical to determine their importance in hypertension. We propose several approaches to aid in these efforts, including: (1) integration of genome-wide association study data with multiomic data sets, including proteomics, transcriptomics, and epigenomics, (2) utilizing linked clinical and genetic data sets to determine genetic contributions to hypertension subphenotypes with distinct drivers, and (3) performing whole exome/genome sequencing on cohorts of individuals with severe hypertension to enrich for rare variants with larger effect sizes. Rather than creating longer lists of hypertension-associated single nucleotide polymorphisms, these approaches are needed to identify key mediators of hypertension pathophysiology.]]> 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 Ripple Effects of Early Life Stress on Vascular Health. Kellum CE, Kelly GC, Pollock JS
Hypertension (Apr 2025)

The term early life stress encompasses traumatic events occurring before the age of 18 years, such as physical abuse, verbal abuse, household dysfunctions, sexual abuse, childhood neglect, child maltreatment, and adverse childhood experiences. Adverse psychological experiences in early life are linked to enduring effects on mental and physical health in adulthood. In this review, we first describe the effects and potential mechanisms of early life stress on the components of the vasculature. Next, we dive into the impact of early life stress on the vasculature across the lifespan through alterations of the epigenetic landscape. Finally, we consolidate the critical gaps in knowledge for focusing future research including the potential for resilience in combatting the impact of early life stress on vascular health.]]> Wed, 31 Dec 1969 19:00:00 EST Cardiac Fibrosis in the Multi-Omics Era: Implications for Heart Failure. Ghazal R, Wang M, Liu D, Tschumperlin DJ, Pereira NL
Circ Res (Mar 2025)

Cardiac fibrosis, a hallmark of heart failure and various cardiomyopathies, represents a complex pathological process that has long challenged therapeutic intervention. High-throughput omics technologies have begun revolutionizing our understanding of the molecular mechanisms driving cardiac fibrosis and are providing unprecedented insights into its heterogeneity and progression. This review provides a comprehensive analysis of how techniques-encompassing genomics, epigenomics, transcriptomics, proteomics, and metabolomics-are providing insight into our understanding of cardiac fibrosis. Genomic studies have identified novel genetic variants and regulatory networks associated with fibrosis susceptibility and progression, and single-cell transcriptomics has unveiled distinct cardiac fibroblast subpopulations with unique molecular signatures. Epigenomic profiling has revealed dynamic chromatin modifications controlling fibroblast activation states, and proteomic analyses have identified novel biomarkers and potential therapeutic targets. Metabolomic studies have uncovered important alterations in cardiac energetics and substrate utilization during fibrotic remodeling. The integration of these multi-omic data sets has led to the identification of previously unrecognized pathogenic mechanisms and potential therapeutic targets, including cell-type-specific interventions and metabolic modulators. We discuss how these advances are driving the development of precision medicine approaches for cardiac fibrosis while highlighting current challenges and future directions in translating multi-omic insights into effective therapeutic strategies. This review provides a systems-level perspective on cardiac fibrosis that may inform the development of more effective, personalized therapeutic approaches for heart failure and related cardiovascular diseases.]]> 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 Exploring omics solutions to reduce micro/nanoplastic toxicity in plants: A comprehensive overview. Arif SM, Khan I, Saeed M, Chaudhari SK, Ghorbanpour M, Hasan M, Mustafa G
Sci Total Environ (Mar 2025)

The proliferation of plastic waste, particularly in the form of microplastics (MPs) and nanoplastics (NPs), has emerged as a significant environmental challenge with profound implications for agricultural ecosystems. These pervasive pollutants accumulate in soil, altering its physicochemical properties and disrupting microbial communities. MPs/NPs can infiltrate plant systems, leading to oxidative stress and cytotoxic effects, which in turn compromise essential physiological functions such as water uptake, nutrient absorption, and photosynthesis. This situation threatens crop yield and health, while also posing risks to human health and food security through potential accumulation in the food chain. Despite increasing awareness of this issue, substantial gaps still remain in our understanding of the physiological and molecular mechanisms that govern plant responses to MP/NP stress. This review employs integrative omics techniques including genomics, transcriptomics, proteomics, metabolomics, and epigenomics to elucidate these responses. High-throughput methodologies have revealed significant genetic and metabolic alterations that enable plants to mitigate the toxicity associated with MPs/NPs. The findings indicate a reconfiguration of metabolic pathways aimed at maintaining cellular homeostasis, activation of antioxidant mechanisms, and modulation of gene expression related to stress responses. Additionally, epigenetic modifications suggest that plants adapt to prolonged plastics exposure, highlighting unexplored avenues for targeted research. By integrating various omics approaches, a comprehensive understanding of molecular interactions and their effects on plant systems can be achieved. This review underscores potential targets for biotechnological and agronomic interventions aimed at enhancing plant resilience by identifying key stress-responsive genes, proteins, and metabolites. Ultimately, this work addresses critical knowledge gaps and highlights the importance of multi-omics strategies in developing sustainable solutions to mitigate the adverse effects of MP/NP pollution in agriculture, thereby ensuring the integrity of food systems and ecosystems.]]> 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 Methylmap: visualization of modified nucleotides for large cohort sizes. Coopman E, D'Hert S, Rademakers R, De Coster W
BMC Bioinformatics (Mar 2025)

Over the years, there has been growing interest in epigenetics, where nucleotide modifications are increasingly recognized for their roles in health and disease. Understanding methylation patterns at the nucleotide level has become pivotal for advancing this field. However, visualizing these modifications, particularly in cohorts of more than a few individuals, remains a challenge.]]> Wed, 31 Dec 1969 19:00:00 EST Genome-wide methylation association study in monozygotic twins discordant for curve severity of adolescent idiopathic scoliosis. Wu Z, Dai Z, Feng Z, Qiu Y, Zhu Z, Xu L
Spine J (Apr 2025)

Emerging evidence suggests that abnormal DNA methylation patterns may play a role in the progression of adolescent idiopathic scoliosis (AIS). However, the mechanisms underlying the influence of DNA methylation on curve severity remain largely unknown.]]> Wed, 31 Dec 1969 19:00:00 EST Improving Cardiovascular Health Through the Consideration of Social Factors in Genetics and Genomics Research: A Scientific Statement From the American Heart Association. Suglia SF, Hidalgo B, Baccarelli AA, Cardenas A, Damrauer S, Johnson A, Key K, Liang M, Magnani JW, Pate B, Sims M, Tajeu GS,  
Circ Cardiovasc Qual Outcomes (Mar 2025)

Cardiovascular health (CVH) is affected by genetic, social, and genomic factors across the life course, yet little research has focused on the interrelationships among them. An extensive body of work has documented the impact of social determinants of health at both the structural and individual levels on CVH, highlighting pathways in which racism, housing, violence, and neighborhood environments adversely affect CVH and contribute to disparities in cardiovascular disease. Genetic factors have also been identified as contributors to risk for cardiovascular disease. Emerging evidence suggests that social factors can interact with genetic susceptibility to affect disease risk. Increasingly, social factors have been shown to affect epigenetic markers such as DNA methylation, which can regulate gene and protein expression. This is a potential biological mechanism through which exposure to poor social determinants of health becomes physically embodied at the molecular level, potentially contributing to the development of suboptimal CVH and chronic disease, thus reinforcing and propagating health disparities. The objective of this statement is to highlight and summarize key literature that has examined the joint associations between social, genetic, and genomic factors and CVH and cardiovascular disease.]]> Wed, 31 Dec 1969 19:00:00 EST Embryo-restricted responses to maternal IL-17A promote neurodevelopmental disorders in mouse offspring. Andruszewski D, Uhlfelder DC, Desiato G, Regen T, Schelmbauer C, Blanfeld M, Scherer L, Radyushkin K, Pozzi D, Waisman A, Mufazalov IA
Mol Psychiatry (Apr 2025)

Prenatal imprinting to interleukin 17A (IL-17A) triggers behavioral disorders in offspring. However, reported models of maternal immune activation utilizing immunostimulants, lack specificity to elucidate the anatomical compartments of IL-17A's action and the distinct behavioral disturbances it causes. By combining transgenic IL-17A overexpression with maternal deficiency in its receptor, we established a novel model of prenatal imprinting to maternal IL-17A (acronym: PRIMA-17 model). This model allowed us to study prenatal imprinting established exclusively through embryo-restricted IL-17A responses. We demonstrated a transfer of transgenic IL-17A across the placental barrier, which triggered the development of selected behavioral deficits in mouse offspring. More specifically, embryonic responses to IL-17A resulted in communicative impairment in early-life measured by reduced numbers of nest retrieval calls. In adulthood, IL-17A-imprinted offspring displayed an increase in anxiety-like behavior. We advocate our PRIMA-17 model as a useful tool to study neurological deficits in mice.]]> Wed, 31 Dec 1969 19:00:00 EST Spatially resolved genome-wide joint profiling of epigenome and transcriptome with spatial-ATAC-RNA-seq and spatial-CUT&Tag-RNA-seq. Li H, Bao S, Farzad N, Qin X, Fung AA, Zhang D, Bai Z, Tao B, Fan R
Nat Protoc (Mar 2025)

The epigenome of a cell is tightly correlated with gene transcription, which controls cell identity and diverse biological activities. Recent advances in spatial technologies have improved our understanding of tissue heterogeneity by analyzing transcriptomics or epigenomics with spatial information preserved, but have been mainly restricted to one molecular layer at a time. Here we present procedures for two spatially resolved sequencing methods, spatial-ATAC-RNA-seq and spatial-CUT&Tag-RNA-seq, that co-profile transcriptome and epigenome genome wide. In both methods, transcriptomic readouts are generated through tissue fixation, permeabilization and in situ reverse transcription. In spatial-ATAC-RNA-seq, Tn5 transposase is used to probe accessible chromatin, and in spatial-CUT&Tag-RNA-seq, the tissue is incubated with primary antibodies that target histone modifications, followed by Protein A-fused Tn5-induced tagmentation. Both methods leverage a microfluidic device that delivers two sets of oligonucleotide barcodes to generate a two-dimensional mosaic of tissue pixels at near single-cell resolution. A spatial-ATAC-RNA-seq or spatial-CUT&Tag-RNA-seq library can be generated in 3-5 d, allowing researchers to simultaneously investigate the transcriptomic landscape and epigenomic landscape of an intact tissue section. This protocol is an extension of our previous spatially resolved epigenome sequencing protocol and provides opportunities in multimodal profiling.]]> Wed, 31 Dec 1969 19:00:00 EST