'; ?> 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, 17 Sep 2025 14:56:07 EDT Wed, 17 Sep 2025 14:56:07 EDT jirtle@radonc.duke.edu james001@jirtle.com A Splice-Region Variant Causes an Atypical Presentation of GNAS Inactivation Disorder. Stone BS, Ramadesikan S, McGinley R, Hickey SE, Dublin-Ryan LB, Estes SI, Elliott VA, Karabasz B, Hunter JM, Chaudhari BP, Wilson RK, Koboldt DC
Am J Med Genet A (Oct 2025)

Pathogenic variants in GNAS can cause a wide range of diseases including pseudohypoparathyroidism, pseudopseudohypoparathyroidism, McCune-Albright syndrome, among others. The specific phenotypic features that may be seen are influenced by the variant type and location in the gene, whether it causes loss or gain of function, and whether it is germline or somatic in nature. The GNAS locus is imprinted, which also results in a parent-of-origin effect. Typically, germline loss of function variants on the maternal allele are associated with variable hormonal resistances, obesity, intrauterine growth restriction, and cognitive impairment. Here, we describe a mother and daughter with a unique splicing variant near exon 5 of the GNAS gene (NM_000516.5:c.432 + 5G>A), shown to cause alternative splicing through RNA sequencing (RNA-seq), likely resulting in a loss-of-function effect. Segregation testing revealed that the variant arose de novo in the mother, and phasing showed it was on her paternal allele. The resultant phenotype includes a SHOX deficiency-like disorder with Madelung deformity in the mother, and significant growth restriction with brachydactyly in the daughter, further expanding the phenotypic spectrum of GNAS inactivation disorders.]]> 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 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 Transcriptomic and epigenomic consequences of heterozygous loss-of-function mutations in AKAP11, a shared risk gene for bipolar disorder and schizophrenia. Farhangdoost N, Liao C, Liu Y, Rochefort D, Aboasali F, Pietrantonio A, Alda M, Dion PA, Chaumette B, Khayachi A, Rouleau GA
Mol Psychiatry (Oct 2025)

The gene A-kinase anchoring protein 11 (AKAP11) recently emerged as a shared risk factor between bipolar disorder and schizophrenia, driven by large-effect loss-of-function (LoF) variants. Recent research has uncovered the neurophysiological characteristics and synapse proteomics profile of Akap11-mutant mouse models. Considering the role of AKAP11 in binding cAMP-dependent protein kinase A (PKA) and mediating phosphorylation of numerous substrates, such as transcription factors and epigenetic regulators, and given that chromatin alterations have been implicated in the brains of patients with bipolar disorder and schizophrenia, it is crucial to uncover the transcriptomic and chromatin dysregulations following the heterozygous knockout of AKAP11, particularly in human neurons. This study uses genome-wide approaches to investigate such aberrations in human induced pluripotent stem cell (iPSC)-derived neurons. We show the impact of heterozygous AKAP11 LoF mutations on the gene expression landscape and profile the DNA methylation and histone acetylation modifications. Altogether we highlight the involvement of aberrant activity of intergenic and intronic enhancers, which are enriched in PBX homeobox 2 (PBX2) and Nuclear Factor-1 (NF1) known binding motifs, respectively, in transcription dysregulations of genes mainly involved in DNA-binding transcription factor activity, actin binding and cytoskeleton regulation, and cytokine receptor binding. We also show significant downregulation of pathways related to ribosome structure and function, a pathway also altered in BD and SCZ post-mortem brain tissues and heterozygous Akap11-KO mice synapse proteomics. A better understanding of the dysregulations resulting from haploinsufficiency in AKAP11 improves our knowledge of the biological roots and pathophysiology of BD and SCZ, paving the way for better therapeutic approaches.]]> 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 Cell-free circulating epigenomic signatures: Non-invasive biomarkers of pregnancy-related outcomes associated with plasticizer exposure. Rajan AK, Mohanty A, Swain P, Tiwari R, Gurjar V, Srivasatava RK, Mishra PK
Reprod Toxicol (Oct 2025)

Globally, plastics have revolutionized industrial and societal advancements, but their durability and low degradability have led to significant environmental pollution. Plasticizers, such as bisphenol A (BPA) and phthalates, are widely used to enhance the flexibility and durability of plastics; however, they are also recognized as endocrine-disrupting chemicals (EDCs) with severe health implications. These chemicals are associated with reproductive toxicity, developmental disruptions, and multigenerational health effects. Recent research has highlighted the impact of plasticizers on irreversible epigenetic modifications, which influence abnormal gene expression patterns without altering the DNA sequence. Histone alterations, DNA methylation, and non-coding RNA regulation are essential pathways. Exposure to BPA and phthalates disrupts these epigenetic processes, leading to long-term reproductive health issues, including infertility, implantation failures, preterm birth, and pregnancy complications such as gestational diabetes and preeclampsia. Cell-free circulating nucleic acids are promising non-invasive biomarkers for the early detection of pregnancy complications, such as preeclampsia, with the potential to predict sensitivity and track gestational age and underlying pathophysiological processes. Combining circulating nucleic acid analysis with evaluations of plasticizer exposure may aid in stratifying high-risk pregnancies. Here, we examined the mechanisms by which plasticizers induce epigenetic alterations, their impact on reproductive health and pregnancy outcomes, and potential biomarkers for identifying these changes to facilitate tailored management of pregnancy complications and assess reproductive health risks.]]> 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 Patient With Prolidase Deficiency due to an Homozygous PEPD Variant, Induced by Paternal Uniparental Isodisomy of Chromosome 19. Carreño-Hidalgo M, Muñoz-Siles R, López-González V, Carreño-Gago L, Dulcet LA
Am J Med Genet A (Oct 2025)

Uniparental disomy (UPD) is a rare phenomenon in which both copies of a chromosome are inherited from a single parent. This can lead to genomic imprinting disorders and recessive disorders due to the presence of recessive pathogenic variants in both alleles. Additionally, depending on the mechanisms by which UPD occurs, mosaic aneuploidies may arise. Here we report the case of a patient with prenatal manifestations of intrauterine growth restriction and polyhydramnios, and postnatal manifestations of multiple congenital anomalies, developmental delay, and facial dysmorphisms. Prenatal exome sequencing targeting the fetal phenotype allowed the detection of uniparental isodisomy of chromosome 19. After birth, exome reanalysis revealed a homozygous pathogenic variant in the PEPD gene. This is the first case of prolidase deficiency due to UPD ever described. Prolidase deficiency is a low-prevalence disease with significant morbidity and mortality. Early diagnosis is essential to provide prognostic information, design an appropriate interdisciplinary follow-up program, and anticipate complications. This case highlights the importance of phenotypic assessment and postnatal clinical follow-up, as well as comprehensive genetic analyses to better understand complex phenotypes.]]> 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 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 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 Dynamic three-dimensional epigenomic reorganization for the development of undifferentiated spermatogonia in mice. Nagano M, Saitou M
Curr Opin Genet Dev (Oct 2025)

Germ cells are unique in their ability to acquire totipotency. Toward this end, they reorganize their three-dimensional (3D) epigenome during their development, including epigenetic reprogramming in primordial germ cells that differentiate mitotic prospermatogonia and ensuing unique epigenetic programming for generating undifferentiated spermatogonia/spermatogonial stem cells (SSCs). Advances in low-input epigenomic and 3D genomic techniques, along with complementary in-depth characterization of scalable in vitro reconstitution systems for germ cell development, that is, in vitro gametogenesis, have elucidated a number of fundamental events during these processes, including insulation augmentation in highly open chromatin following epigenetic reprogramming in mitotic prospermatogonia and insulation erasure and further euchromatization accompanied by chromosomal radial repositioning in undifferentiated spermatogonia/SSCs. These 3D epigenomic organizations likely serve as a foundation for generating fully functional gametes. Elucidating the mechanisms underlying 3D epigenomic reorganization during germ cell development will be instrumental not only for understanding the basis for totipotency but also for further advancing in vitro gametogenesis.]]> 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 Transgenerational effects and mechanisms of nano-SiO on pulmonary. Chu J, Liu C, Chen S, Yang Y, Zhang K, Fu Y, Yuan B, Wang Z
Reprod Toxicol (Oct 2025)

Nanomaterials, such as nano-SiO, have been extensively studied and applied in various fields. However, little is known about the transgenerational effects of nano-SiO. The purpose of this study was to investigate the transgenerational effects and mechanisms of paternal nano-SiO exposure on the lung of male offspring. Male C57BL/6 mice were exposed to nano-SiO, which were then mated with unexposed females to produce F1 and F2 generations. The effects of nano-SiO were evaluated over two generations (F0 and F2) by determining pulmonary function, lung tissue pathology, and analyzing the imprinted gene expression and DNA methylation profile in lung tissues. The results showed that tidal volume (VT), 1/2 tidal volume flow (EF50), peak expiratory flow (PEF), peak inspiratory flow (PIF), and minute ventilation (MV) increased significantly in both the F0 and F2 generations. Moreover, HE staining of lung tissues showed inflammation of the F0. PCR results of lung tissues imply a significant change in the expression of Dlk1 and Dio3. Furthermore, nano-SiO exposure increased the methylation levels of Dlk1 and Dio3 across generations F0 and F2. Overall, nano-SiO exposure detrimentally impacts lung respiratory function in male mice by modulating the epigenetic regulation of Dlk1-Dio3 imprinted genes, potentially leading to transgenerational risks. However, further studies are needed to determine the long-term physiological consequences in adulthood.]]> 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 Differences in gene expression patterns between parthenogenetically and sexually produced offspring during early development of Reticulitermes speratus. Kamiyama R, Takahashi M, Takata M, Matsuura K
Insect Mol Biol (Oct 2025)

Social insects exhibit reproductive division of labour, governed by both external and internal factors influencing caste determination. In termites with a unique reproductive system known as asexual queen succession (AQS), queens produce neotenic queens via parthenogenesis, while workers and alates arise through sexual reproduction. This inherent caste differentiation bias may have resulted from differences in gene expression potentially influenced by the parent-of-origin effect, as parthenogenetic daughters inherit only maternal genomes, while sexually produced daughters inherit both paternal and maternal genomes. Here, we show that gene expression patterns in developing embryos of the termite Reticulitermes speratus differ significantly between parthenogenetic and sexually produced offspring. However, SNP analysis indicated that these differences were not attributable to the parent-of-origin effect. Through RNA-seq analysis of female embryos post-katatrepsis, we identified 21 genes, including jhbp, nlk, and wge, which are known to be involved in caste differentiation and morphogenesis, with significant expression differences between parthenogenetic and sexually produced daughters. SNP analysis of sexually produced embryos did not reveal any parent-of-origin biased expression except for mitochondrial genes, though 12 genes exhibited colony-specific expression patterns. These findings suggested that early developmental gene expression partly explained caste differentiation biases. Further research is essential to elucidate the molecular mechanisms behind these transgenerational effects, providing insight into the evolution of AQS and complex caste determination in social insects from a gene expression perspective.]]> 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 Designing Epigenetic Clocks for Wildlife Research. Newediuk L, Richardson ES, Bohart AM, Roberto-Charron A, Garroway CJ, Jones MJ
Mol Ecol Resour (Oct 2025)

The applications of epigenetic clocks - statistical models that predict an individual's age based on DNA methylation patterns - are expanding in wildlife conservation and management. This growing interest highlights the need for field-specific design best practices. Here, we provide recommendations for two main applications of wildlife epigenetic clocks: estimating the unknown ages of individuals and assessing their biological ageing rates. Epigenetic clocks were originally developed to measure biological ageing rates of human tissues, which presents challenges for their adoption in wildlife research. Most notably, the estimated chronological ages of sampled wildlife can be unreliable, and sampling restrictions limit the number and variety of tissues with which epigenetic clocks can be constructed, reducing their accuracy. To address these challenges, we present a detailed workflow for designing, validating applying accurate wildlife epigenetic clocks. Using simulations and analyses applied to an extensive polar bear dataset from across the Canadian Arctic, we demonstrate that accurate epigenetic clocks for wildlife can be constructed and validated using a limited number of samples, accommodating projects with small budgets and sampling constraints. The concerns we address are critical for clock design, whether researchers or third-party service providers perform the bioinformatics. With our workflow and examples, we hope to support the accessible and widespread use of epigenetic clocks in wildlife conservation and management.]]> 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 A stem cell-based toolkit to model Angelman syndrome caused by paternal uniparental disomy of chromosome 15. Cazaux Mateus F, Camões Dos Santos J, Arez M, Bekman EP, da Rocha ST
Hum Cell (Sep 2025)

Angelman syndrome is a rare neurodevelopmental disorder caused by the loss of function of the maternally inherited UBE3A gene within the chr15q11-q13 region. This gene is subjected to a tissue-specific form of genomic imprinting leading to the silencing of the paternal allele in neurons. Angelman syndrome can result from various (epi)genetic mechanisms, with paternal uniparental disomy of chromosome 15 (patUPD15) being one of the rarest and least studied due to the absence of suitable models. To address this gap, we generated three independent induced pluripotent stem cell (iPSC) lines from individuals with Angelman syndrome caused by patUPD15, alongside genetically matched unaffected familial controls. Peripheral blood mononuclear cells (PBMCs) were reprogrammed into iPSCs using a non-integrative Sendai virus-based approach expressing the Yamanaka factors. All iPSC lines underwent rigorous quality control, confirming stem cell identity, trilineage differentiation potential, and genetic and epigenetic integrity. This newly established iPSC toolkit provides a powerful platform to investigate the molecular underpinnings of Angelman syndrome caused by patUPD15, paving the way for future translational research and therapeutic development tailored for this understudied form of the disorder.]]> Wed, 31 Dec 1969 19:00:00 EST