'; ?> 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 Wed, 01 Oct 2025 16:31:42 EDT Wed, 01 Oct 2025 16:31:42 EDT jirtle@radonc.duke.edu james001@jirtle.com Elucidating the genetic architecture of early menopause in the Tehran cardiometabolic genetic study. Najd-Hassan-Bonab L, Motafeghi F, Moazzam-Jazi M, Farahmand M, Azizi F, Daneshpour MS, Ramezani Tehrani F
Maturitas (Oct 2025)

Population studies elucidating the genetic architecture of early menopause have mainly focused on European ancestries, leaving a gap in understanding of the genetic influences in non-European populations. This study seeks to identify potential genetic variants linked to early menopause in Iranian women.]]> Wed, 31 Dec 1969 19:00:00 EST Transient alterations in nucleosome distribution and sensitivity to nuclease define the THP-1 monocyte-to-macrophage transition. Benoit JM, Buck BD, Khadem M, Bass HW, Dennis JH
J Leukoc Biol (Oct 2025)

The monocyte-to-macrophage transition is marked by alterations to both the structure and function of the genome, including changes in histone posttranslational modifications, DNA methylation, 3D nuclear architecture, and expression of lineage specific genes. The nucleosome is the fundamental organizational unit of the eukaryotic genome and underpins both genome structure and function. However, nucleosome dynamics at promoters, which are essential for transcriptional regulation, are understudied in cellular differentiation. We conducted high-resolution chromatin structure profiling at promoters in the THP-1 cell line at 8 different time points spanning phorbol-12-myristate 13-acetate (PMA)-induced monocyte-to-macrophage differentiation. We found that fewer than 10% of nucleosomes within promoters were redistributed during differentiation and only a subset of these were associated with immediate transcriptional alterations. Nucleosomes within the promoters of PMA-responsive genes were strongly positioned prior to differentiation and experienced minimal alterations during differentiation, thus implying the existence of a predifferentiation primed chromatin state. Additionally, we observed pronounced alterations in nucleosome sensitivity to MNase digestion within 1 h of PMA-induced differentiation and the emergence of a highly resistant phenotype in fully differentiated cells. We found that resistance is correlated with active chromatin marks, transcription factor binding, gene expression, and higher-order chromatin structure, demonstrating that it is a useful measure of both genome structure and function. Together, this suggests that, unlike more stable nucleosome distribution, transient sensitivity alterations may underpin new genomic functions in differentiating cells. Our results offer a framework for understanding how chromatin structural alterations potentiate cellular differentiation in a monocyte model and use methodology that is widely applicable to other systems.]]> Wed, 31 Dec 1969 19:00:00 EST Sex-stratified piRNA expression analysis reveals shared functional impacts of perinatal lead (Pb) exposure in murine hearts. Sala-Hamrick KE, Wang K, Perera BPU, Sartor MA, Svoboda LK, Dolinoy DC
Epigenetics (Dec 2025)

The landscape of PIWI-interacting RNA (piRNA) expression in the heart is poorly understood, particularly regarding sex differences. Altered piRNA expression has been reported in cardiovascular disease (CVD), and although exposure to the metal lead (Pb) is strongly associated with CVD risk, no studies have investigated Pb's effects on cardiac piRNAs. This study aimed to characterize piRNA expression in the murine heart and assess sex-specific effects of human-relevant maternal Pb exposure on adult offspring cardiac piRNA expression. piRNAs were identified from whole mouse hearts using sodium periodate exclusion of small RNA and subsequent sequencing. Control mice expressed 18,956 piRNAs in combined-sex analysis; sex-specific analyses revealed 9,231 piRNAs in female hearts and 5,972 piRNAs in male hearts. Genomic mapping showed 28-41% aligned to introns, while 12-28% mapped to exons. Comparing control and Pb-exposed hearts, we found more potential Pb-induced expression changes in females (847) compared to males (187) (p-value < 0.05 and |logFC| > 1). These piRNAs were significantly enriched near genes involved in biological processes related to heart function and CVD development, including mitochondrial function, energy metabolism, and cardiac muscle structure (FDR < 0.05). Overall, we characterized combined and sex-stratified piRNA expression in both control and Pb-exposed murine hearts. In addition to providing a foundation for sex-specific piRNA expression in the heart, these findings suggest a novel epigenetic mechanism by which developmental Pb exposure may impact CVD risk later in life. Future studies will link these sex-specific molecular changes to Pb-induced alterations in cardiac function.]]> Wed, 31 Dec 1969 19:00:00 EST Rapid origin and turnover of genomic imprinting by transposable elements. Del Toro-De León G, Köhler C
Curr Opin Plant Biol (Oct 2025)

Genomic imprinting, the preferential expression of alleles based on their parent-of-origin, is an epigenetic mechanism that plays a key role in endosperm development and establishment of hybridization barriers. While imprinting is frequently associated with DNA methylation asymmetries and transposable elements (TEs), growing evidence suggests that this connection is not applying to all imprinted genes. This review synthesizes recent findings across different plant species, highlighting how TEs not only initiate imprinting through epigenetic reprogramming but also participate in its turnover, driving rapid evolutionary changes. We discuss the contribution of chromatin context to imprinting, and the emerging evidence of imprinting mechanisms independent of DNA methylation and TEs. We propose a dynamic and lineage-specific regulation of imprinting shaped by epigenetic context, TE activity, and developmental timing.]]> Wed, 31 Dec 1969 19:00:00 EST and are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation. Daskeviciute D, Sainty B, Chappell-Maor L, Bone C, Russell S, Iglesias-Platas I, Arnaud P, Monteagudo-Sánchez A, Greenberg MVC, Chen K, Manerao-Azua A, Perez de Nanclares G, Lartey J, Monk D
Epigenetics (Dec 2025)

Genomic imprinting is the parent-of-origin specific monoallelic expression of genes that result from complex epigenetic interactions. It is often achieved by monoallelic 5-methylcytosine, resulting in the formation of differentially methylated regions (DMRs). These show a bias towards oocyte-derived methylation and survive reprogramming in the pre-implantation embryo. Imprinting is widespread in the human placenta. We have recently performed whole-genome screens for novel imprinted placenta-specific germline DMRs (gDMRs) by comparing methylomes of gametes, blastocysts and various somatic tissues, including placenta. We observe that, unlike conventional imprinting, for which methylation at gDMRs is observed in all tissues, placenta-specific imprinting is associated with transient gDMRs, present only in the pre-implantation embryo and extra-embryonic lineages. To expand the list of imprinted genes subject to placenta-specific imprinting, we reinvestigated our list of candidate loci and characterized two novel imprinted genes, and , both of which display polymorphic imprinting. Interrogation of placenta single-cell RNA-seq datasets, as well as cell-type methylation profiles, revealed complex cell-type specificity. We further interrogated their methylation and expression in placental samples from complicated pregnancies, but failed to identify differences between intrauterine growth restricted or pre-eclamptic samples and controls, suggesting they are not involved in these conditions.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic imprinting in innate lymphoid cell precursors directs the lineage segregation of innate lymphoid cells. Liu Z, Shao F, Zhang Q, Zhao M, Gao S, Zhang X, Yu D, Zhang J, Xia P, Wang S
Nat Immunol (Oct 2025)

Innate lymphoid cells (ILCs) are essential for mucosal homeostasis, but the epigenetic regulation of their lineage segregation remains elusive. Here we simultaneously profiled the single-cell DNA methylome, chromatin accessibility and transcriptome of ILC subsets and ILC precursors (ILCPs) and found that ILCPs could be divided into two subgroups (ILCP1 and ILCP2). ILCP2s had highly heterogeneous DNA methylation profiles and could be divided into three groups according to their DNA methylation characteristics, which matched those of ILC subsets. We identified the signature methylation regions (SMRs) of each ILC subset and traced the DNA methylation imprinting during ILCP differentiation. ILCP2s with hypomethylated SMRs characteristic of ILC subsets differentiated into those subsets. DNA methylation editing of SMRs suppressed ILC lineage segregation, while deletion of Dnmt1 in ILCPs abrogated the heterogeneous distribution of SMRs and resulted in ILC differentiation defects. These findings provide evidence that epigenetic imprinting determines lineage segregation during immune cell development.]]> Wed, 31 Dec 1969 19:00:00 EST The myoblast methylome: multiple types of associations with chromatin and transcription. Sen S, Lacey M, Baribault C, Ponnaluri VKC, Esteve PO, Ehrlich KC, Meletta M, Pradhan S, Ehrlich M
Epigenetics (Dec 2025)

Epigenetic changes are implicated in development, repair, and physiology of postnatal skeletal muscle (SkM). We generated methylomes for human myoblasts (SkM progenitor cells) and determined myoblast differentially methylated regions (DMRs) for comparison to the epigenomics and transcriptomics of diverse cell types. Analyses were from global genomic and single-gene perspectives and included reporter gene assays. One atypical finding was the association of promoter-adjacent hypermethylation in myoblasts with transcription turn-on, but at downmodulated levels, for certain genes (., and ). In contrast, brain-specific was in repressed chromatin and silent in most cell types but linked to hypermethylated DMRs specifically in myoblasts. The -linked DMRs might be needed because of the overlapping or nearby binding of myogenic differentiation protein 1 (MYOD). We found genome-wide overlap of DMRs with MYOD or CCCTC-binding factor (CTCF) binding sites in myoblasts that is consistent with the importance of MYOD, as well as CTCF, in organizing myoblast transcription-enhancing chromatin interactions. We also observed some gene upregulation correlated with a special association of regional DNA hypomethylation with H3K36me3, H3K27ac, and H3K4me1 enrichment. Our study highlights unusual relationships between epigenetics and gene expression that illustrate the interplay between DNA methylation and chromatin epigenetics in the regulation of transcription.]]> Wed, 31 Dec 1969 19:00:00 EST Multi-omics profiling reveals two distinct trajectories in the progression from mild cognitive impairment to Alzheimer's disease. Guo X, Fu H, Qin M, Kan J,  
J Alzheimers Dis (Oct 2025)

BackgroundAlzheimer's disease (AD) exhibits significant clinical and pathological heterogeneity, particularly during the mild cognitive impairment (MCI) transitional stage. Current understanding of the molecular drivers underlying distinct MCI progression trajectories remains incomplete, hindering the development of personalized interventions.ObjectiveThis study aims to integrate transcriptomic, epigenomic, and metabolomic data to identify distinct trajectories in the progression from MCI to AD, and to explore the underlying disease heterogeneity.MethodsWe integrated transcriptomic, epigenomic, and metabolomic data from MCI patients to model the progression to AD and stratified them into subtypes. We then examined molecular differences between MCI and AD within each subtype, identifying key immune microenvironments and regulatory pathways via immune cell infiltration analysis, WGCNA, and GO/KEGG analyses. Finally, we applied Cox regression to identify prognostic biomarkers and built a random forest prognostic model.ResultsOur analysis identified two distinct MCI-to-AD progression subtypes. Subtype 1 was marked by metabolic dysregulation and slower cognitive decline, while Subtype 2 was driven by chronic immune activation and exhibited faster cognitive decline. The trajectory subtypes captured molecular perturbations that were missed by traditional unclustered methods. Prognostic models based on these molecular signatures predicted disease progression over 1-5 years, with AUROC values ranging from 0.851 to 0.893 for Subtype 1 and from 0.878 to 0.927 for Subtype 2.ConclusionsOur findings highlight the importance of multi-omics trajectory stratification in understanding the heterogeneity of AD progression. The identification of two distinct progression trajectories provides insights into the underlying mechanisms of AD.]]> Wed, 31 Dec 1969 19:00:00 EST Differential methylation patterns in cord blood associated with prenatal exposure to neighborhood crime: an epigenome-wide association study and regional analysis. Martin CL, Chen J, D'Alessio AS, Ward-Caviness CK, Ye A, Lodge EK, Ghastine L, Dhingra R, Jima DD, Murphy SK, Hoyo C
Epigenetics (Dec 2025)

Exposure to prenatal social stressors during pregnancy is associated with adverse birth outcomes and has been linked to epigenetic changes in DNA methylation (DNAm); however, less understood is the effect of neighborhood-level stressors like crime during pregnancy on offspring DNAm. Using data from the Newborn Epigenetic Study, we conducted epigenome-wide and regional analyses of the association between exposure to neighborhood crime and DNAm in offspring cord blood using Illumina's HumanMethylation450k BeadChip among 185 mother-offspring pairs. Prenatal exposure to neighborhood crime at the census block group level was mapped to participants' residential addresses during the gestational window from the date of last menstrual period to delivery. Models for the epigenome-wide and regional analyses were adjusted for maternal age, race/ethnicity, education, smoking, cell-type composition, and offspring sex. Genetic influence and gene expression enrichment were assessed using methylation quantitative trait loci (mQTLs) and expression quantitative trait methylation (eQTMs) analyses. Functional enrichment was determined using Gene Ontology and KEGG databases. We did not find evidence of epigenome-wide associations between prenatal neighborhood crime exposure and DNAm; however, we identified nine differentially methylated regions (DMRs) comprising 51 CpG sites associated with neighborhood crime. CpG sites within significant differentially methylated regions were associated with mQTLs at birth and eQTMs upon further examination. KEGG analysis identified a significant Th1 and Th2 cell differentiation pathway. Our results suggest potential links between prenatal neighborhood crime exposure and offspring DNAm; however, additional research is needed in larger cohorts across wider geographic areas to confirm our results.]]> Wed, 31 Dec 1969 19:00:00 EST Using Epigenetic Data to Deconvolute Immune Cells in Cancer from Blood Samples. Boughanem H, Ouzounis S, Callari M, Sanz-Pamplona R, Macias-Gonzalez M, Katsila T
Methods Mol Biol (2026)

DNA methylation plays a crucial role in regulating gene expression and is a hallmark of epigenetic dysregulation in human tumors. High-throughput DNA methylation profiling can unravel intricate patterns in cancer. Moreover, understanding immune cell dynamics is essential for comprehending cancer progression and treatment response. Using DNA methylation data in immune cells, we can apply deconvolution algorithms estimate proportions of major immune cell types, providing insights into immune status and its implications in cancer. Functional analysis can identify specific overrepresented or underrepresented immune cell subsets, potentially uncovering novel biomarkers or therapeutic targets. This pipeline presents a detailed workflow in RStudio for DNA methylation studies and immune cell deconvolution, enhancing reproducibility and efficiency. The workflow integrates preprocessing, analysis, and visualization steps, facilitating robust inference of cell-type proportions from DNA methylation data.]]> Wed, 31 Dec 1969 19:00:00 EST use capsules, transporters, mobile genetic elements, and other evolutionary adaptations to survive antibiotics exposure in the absence of resistance genes. Mmatli M, Mbelle NM, Fourie B, Osei Sekyere J
Virulence (Dec 2025)

Whole-genome sequencing, transcriptomic profiling, and epigenomic analyses were performed. Phenotypic assays were used to evaluate the effects of various inhibitors on antibiotic susceptibility, while bioinformatic pipelines were used to characterize resistance determinants, virulence factors, and mobile genetic elements (MGEs).]]> Wed, 31 Dec 1969 19:00:00 EST An interview with Azim Surani. Moffett A, Jowett GM
Development (Oct 2025)

Professor Azim Surani is the Director of Epigenomics and Germline Imprinting at the Gurdon Institute in Cambridge, UK. He is this year's recipient of both the prestigious Kyoto Prize and the Paul Ehrlich and Ludwig Darmstaedter prize, recognising his contributions to the discovery of genomic imprinting, the foundation of the modern field of epigenetics. In honour of the 40th anniversary of this seminal work, a Festschrift meeting was held at King's College, Cambridge, UK, titled 'Imprinting, Germlines, and how we got here'. In addition to the meeting notes, we interviewed Professor Surani about his non-traditional and inspirational route into academia.]]> 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 Clinical translation of ctDNA epigenetic signatures in lung cancer: An integrated strategy for early detection, therapeutic guidance, and prognostic stratification. You JB, Shen SM, Fan JH, Zhen SS, Sha JM
Biochem Biophys Res Commun (Oct 2025)

Liquid biopsy, particularly through the analysis of circulating tumor DNA (ctDNA) epigenetic signatures, is revolutionizing lung cancer management. This comprehensive review examines the pivotal role of DNA methylation, histone modifications, and non-coding RNAs in ctDNA for early detection, therapeutic monitoring, and prognostic prediction. We critically evaluate emerging technologies, including nanopore sequencing and microfluidic platforms, which address the sensitivity-specificity trade-offs inherent in current methodologies, and emphasize the imperative for standardized workflows. Through the integration of multi-omics data and single-cell epigenomics, we propose a comprehensive roadmap for clinical translation. Additionally, we discuss the ethical and regulatory challenges associated with global implementation of liquid biopsy. This review provides an in-depth analysis of the current state and future directions of ctDNA epigenetic markers in lung cancer management, offering strategic insights for optimizing detection technologies and enhancing clinical applications.]]> Wed, 31 Dec 1969 19:00:00 EST Optimized CUT&Tag enables robust epigenome profiling in Schizosaccharomyces pombe. Huang CZ, Zhou KD, Ma W
Methods (Nov 2025)

We optimized permeabilization for CUT&Tag in S. pombe, enabling robust H3K9me3 profiling using lightly fixed permeabilized sepheroplasts, overcoming limitations of ChIP-seq including crosslinking artifacts and high cell input. We established an optimized Cleavage Under Targets and Tagmentation (CUT&Tag) protocol for high-resolution epigenome profiling inSchizosaccharomyces pombeusing Critical permeabilization refinements identified Lywallzyme as the optimal enzyme for spheroplast generation (>95 % efficiency in 60 min at 10 mg/mL), outperforming Zymolyase-20 T and combinatorial treatments. Systematic parameter optimization revealed concentration-dependent digestion kinetics and an inverse cell load-efficiency relationship (5 × 10 cells achieving > 90 % conversion in 50 min at 5 mg/mL). Validated through H3K9me3 mapping in wild-type andclr4Δstrains (10⁶ cells/replicate), this approach captured specific heterochromatic enrichment at centromeres/telomeres with complete signal ablation in mutants, while reduced spike-in DNA (0.2 pg) significantly enhanced signal-to-noise ratios. The protocol enables robust epigenomic analysis with minimal cell input and enhanced resolution.]]> Wed, 31 Dec 1969 19:00:00 EST Novel approaches and applications in identifying DNA methylation markers of cardio-kidney-metabolic disease. Liu C, Young A, Abi N, Chen J, Fernandes Gyorfy M, Li Y, Sun S, Zhou JJ, Sun YV
Epigenomics (Oct 2025)

Cardio-kidney-metabolic (CKM) diseases represent a major public health challenge, accounting for a large proportion of global burden of morbidity and mortality. These conditions share risk factors, including genetic predisposition, environmental exposures, and lifestyle influences, which collectively drive disease development and progression. Epigenetic modifications, particularly DNA methylation (DNAm), serve as key mediators and biomarkers between these risk factors and disease phenotypes by regulating gene expression without altering the DNA sequence. Epigenome-wide association studies have identified DNAm markers associated with CKM diseases and related phenotypes, highlighting both shared pathways and disease-specific epigenetic signatures in inflammation, metabolic dysfunction, and aging-related processes. Longitudinal studies further demonstrate the dynamic nature of DNAm changes over time, offering insights into disease trajectories. Additionally, methylation risk scores integrating multiple epigenetic markers show promise in improving disease prediction and risk stratification beyond traditional clinical factors. To synthesize the current evidence, we conducted a targeted literature search in PubMed for English-language, peer-reviewed articles published between 2014 and the present. Future research leveraging large, well-phenotyped cohorts, advanced statistical methods, and innovative study designs will be critical for uncovering novel biomarkers, refining risk prediction models, and developing targeted epigenetic therapies to mitigate the global burden.]]> Wed, 31 Dec 1969 19:00:00 EST Perfluoroalkyl substance pollutants disrupt microglia function and trigger transcriptional and epigenomic changes. Cheng Y, Li JR, Yu H, Li S, Tychhon B, Cheng C, Weng YL
Toxicology (Nov 2025)

Per- and polyfluoroalkyl substances (PFAS), commonly referred to as "forever chemicals", are widely utilized in various industries and consumer products worldwide. Their exposure has been associated with numerous diseases and malignancies, including neurodevelopmental and neurodegenerative disorders. However, the molecular mechanisms underlying PFAS-induced adverse effects on the central nervous system (CNS) remain poorly understood. In this study, we investigated the transcriptomic and epigenetic changes in microglia exposed to perfluorooctane sulfonate (PFOS), a prevalent PFAS compound. Our findings demonstrate that 24-hour PFOS exposure (25 and 50 µM) disrupts the microglial transcriptome and compromises their homeostatic state, marked by increased inflammation and impaired actin cytoskeleton remodeling. Comparative analysis with in vivo transcriptional states revealed that PFOS-exposed microglia exhibit gene expression profiles resembling those of aged microglia. Additionally, profiling of active chromatin regions uncovered significant alterations in the H3K27ac landscape in PFOS-exposed microglia. Notably, these epigenetic disruptions persisted even after PFOS withdrawal, with a subset of H3K27ac-enriched regions remaining altered, suggesting the presence of lasting epigenetic scars. Furthermore, transcription factor analysis implicated the AP-1 and TEAD families as potential upstream regulators connecting the altered chromatin landscape to transcriptomic changes. Collectively, these findings provide mechanistic insights into how PFOS exposure disrupts microglial function and highlight its potential role in exacerbating neurodegenerative processes.]]> Wed, 31 Dec 1969 19:00:00 EST The sex-chromosomes related cellular dimorphism in physiology and pathology. Antinozzi C, Sgrò P, Di Luigi L
Mol Cell Endocrinol (Oct 2025)

Sex-based biological differences have a profound impact on health and disease. Historically, these disparities were primarily attributed to differences in gonadal hormones. Recent advances in biochemistry and molecular biology, however, have revealed additional contributing mechanisms-most notably, the critical role of genes located on the X and Y chromosomes. The expression of Y-linked genes, increased dosage of X-linked genes in XX compared to XY cells due to incomplete X-chromosome inactivation, genomic imprinting, and the presence of non-coding and micro-RNAs on the X chromosome are all factors that require consideration in the development of in vitro models addressing sex dimorphism. In the present narrative review, we propose studies showing sex differences in vascular and cardiac cells, skeletal muscle cells, adipose tissue, liver, immune cells, cancer tissues and brain tissues. Given the absence of appropriate experimental methodologies for reproducing in vitro the sex differences observed in vivo and the limited research conducted at the cellular and molecular level to elucidate the mechanisms responsible for the observed dimorphism, the present review has two objectives. Firstly, it aims to emphasize the necessity of incorporating sex as a variable in preclinical research. Secondly, it highlights the importance of sex chromosome differences as a biological variable that can influence cell physiology and biological responses, which is crucial when conducting in vitro studies.]]> Wed, 31 Dec 1969 19:00:00 EST Study on the pathogenesis of vascular dementia by gene expression regulatory network. Bai H
Gene (Oct 2025)

Vascular dementia (VaD) is the second largest type of dementia in the world after Alzheimer's disease, characterized by selective loss of neurons caused by cerebrovascular disease, dysfunction of cortical subcortical circuits, and cognitive domain specific damage. This article systematically analyzes some gene expression regulation issues in VaD pathogenesis from five dimensions: abnormal gene expression profile, epigenetic modification abnormality, transcription factor (TF) cascade regulation, non coding RNA (ncRNA) regulatory axis disorder, and gene environment interaction. For the first time, the "Dynamic Imbalance Theory of Gene Regulation Network" (DIGRN) is proposed. By integrating transcriptomics, epigenomics, proteomics, and clinical sample analysis, the key roles of abnormal DNA methylation, histone modification imbalance, transcription factor cascade activation, miRNA lncRNA regulatory axis disruption, and synergistic effects of environmental factors in VaD pathology were revealed. The DIGRN theory provides a new framework for early diagnosis, molecular typing, and targeted intervention of VaD. Its clinical translation prospects involve epigenetic drug development, ncRNA biomarker screening, and construction of gene environment interaction risk prediction models.]]> Wed, 31 Dec 1969 19:00:00 EST Maternal imprinting of autoreactivity in a murine model of systemic lupus erythematosus. Fonager SV, Winther G, Weber YCL, Wittenborn TR, Kastberg KS, Terczyńska-Dyla E, Jensen L, Hansen LA, Carroll MC, Luo Y, Lin L, Degn SE
Brain Behav Immun (Oct 2025)

Mammals confer passive immunity upon their offspring via transplacental IgG and postnatal transfer of milk IgA. Maternofetal microchimerism and the cytokine environment in utero may also influence the developing offspring. Normally protective maternal immune factors can adversely affect the offspring in the context of maternal autoimmune disease. Here, unexpectedly, we observed maternal imprinting of autoreactivity, presenting as spontaneous germinal centers (GCs) and endogenous autoantibody production, in a murine model of systemic lupus erythematosus (SLE). This prompted us to investigate how maternal autoimmune status can influence the offspring independently of genetic factors. Using embryo transfers to experimentally uncouple genetic from environmental maternal factors, we did not observe maternofetal microchimerism, but embryo transfer offspring of autoimmune dams received maternally derived IgG2A and anti-dsDNA antibodies. Moreover, they displayed increased formation of spontaneous GCs and elevated endogenous IgG2C autoantibody production. The neuroimmunological phenotype in offspring appeared unaffected. Taken together, our findings suggest maternal immune factors actively contribute to shape the susceptibility of offspring to autoimmune diseases independent of genetic factors.]]> Wed, 31 Dec 1969 19:00:00 EST