'; ?> 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 Thu, 18 Dec 2025 23:21:44 EST Thu, 18 Dec 2025 23:21:44 EST jirtle@radonc.duke.edu james001@jirtle.com Reconstructing epigenomic dynamics through a single-cell multi-epigenome data integration framework. Fujii T, Tomimatsu K, Kato M, Ito M, Sato S, Kurumizaka H, Sato Y, Maehara K, Kimura H, Harada A, Ohkawa Y
Nat Commun (Dec 2025)

Transcriptional regulation arises from the dynamic and combinatorial actions of multiple regulatory factors on genomic DNA. Although many epigenomic regulators have been identified, the precise order in which these factors accumulate at individual gene loci to activate transcription remains unclear. Here we show a single-cell data integration framework that infers the binding order of multiple chromatin factors at single-cell resolution. Central to this framework is sci-mtChIL-seq, a scalable single-cell method that simultaneously profiles genome-wide binding of RNA polymerase II (RNAPII) and diverse epigenomic regulators. By defining transcriptional states through RNAPII occupancy and integrating multiple sci-mtChIL-seq datasets, we systematically link the combinatorial patterns of transcription factor binding, histone modifications and chromatin remodeling. This framework reveals the temporal coordination among chromatin factors during transcriptional activation, providing a powerful approach to uncover context-dependent epigenomic dynamics and the principles of gene regulation in complex cellular systems.]]> 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 A hitchhiker's guide to single-cell epigenomics: Methods and applications for cancer research. Moreno-Gonzalez M, Sierra I, Kind J
Int J Cancer (Jan 2026)

Genetic mutations are well known to influence tumorigenesis, tumor progression, treatment response and relapse, but the role of epigenetic variation in cancer progression is still largely unexplored. The lack of epigenetic understanding in cancer evolution is in part due to the limited availability of methods to examine such a heterogeneous disease. However, in the last decade the development of several single-cell methods to profile diverse chromatin features (chromatin accessibility, histone modifications, DNA methylation, etc.) has propelled the study of cancer epigenomics. In this review, we detail the current landscape of single-omic and multi-omic single-cell methods with a particular focus on the examination of histone modifications. Furthermore, we provide recommendations on both the application of these methods to cancer research and how to perform initial computational analyses. Together, this review serves as a referential framework for incorporating single-cell methods as an important tool for tumor biology.]]> Wed, 31 Dec 1969 19:00:00 EST Integrative Multi-Adaptive Biological-Mental-Social Network Modeling of Changing Social and Organizational Contexts, Epigenetics, Personality Traits and Burnout Dimensions. Bouma D, Treur J, Hendrikse SCF
Int J Neural Syst (Dec 2025)

This research addresses the interplay of changing social and organizational context factors with the big five personality traits and the three main characterizing elements of burnout. A computational analysis is contributed based on an integrative biological-mental-social network modeling approach. The simulation results show how two people who are high in personality traits such as agreeableness, openness, extraversion, conscientiousness, and highly sensitive to neuroticism, are vulnerable to reaching a burnout level in all dimensions whenever the organizational context is changing in a less favorable direction. By a What-If analysis, it is analyzed how important characteristics affect the outcomes and indicate how, in a qualitative sense, that is in line with empirical literature. Several differentiations are made. In particular, the connection between the three dimensions of burnout shows that it is possible that one employee reaches a burnout state while the other does not. It is also shown how therapy alone may not be sufficient as a long-term treatment, but therapy of one employee does affect the other. As numerical data are not (yet) available, further numerical validation has been proposed for future work.]]> Wed, 31 Dec 1969 19:00:00 EST Genetic and epigenetic insights into systemic lupus erythematosus: linking long non-coding RNA growth arrest-specific transcript 5 and interferon signature. Maghraby GG, El-Menyawi MA, Rehiem HAA, Shaker OG, Habib MM, Elgohary R
J Rheum Dis (Jan 2026)

Interferon (IFN) signaling, and excessive apoptosis have a well-established role in systemic lupus erythematosus (SLE) pathogenesis. Long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) has been linked to excessive apoptosis and upregulation of IFN genes. We aimed to investigate the expression of IFN-stimulated genes in SLE patients compared to healthy controls, and to assess their association with lncRNA GAS5 and clinical characteristics of SLE.]]> Wed, 31 Dec 1969 19:00:00 EST Integration of omics data in the diagnosis and therapy of glioblastoma. Möller C, Schoof M, Ligon KL, Schüller U
Brain Pathol (Jan 2026)

Since the 2016 update of the WHO Classification of Tumors of the Central Nervous System, omics data have been officially integrated into the diagnostic process for glioblastoma, the most prevalent and aggressive primary malignant brain tumor in adults. This review will examine the current and future integration of omics data in both the diagnosis and therapy of glioblastomas. The current clinical use of omics data primarily focuses on genomics for determining the IDH- and H3-wildtype status of the tumor, and on epigenomics, such as assessing MGMT promoter methylation status as a prognostic and predictive biomarker. However, it can be anticipated that the usage and importance of omics data will likely increase in the future. This work highlights how omics technologies have significantly enhanced our understanding of glioblastoma, particularly of its extensive heterogeneity. This enhanced understanding has not only improved diagnostic accuracy but has also facilitated the identification of new predictive and/or prognostic biomarkers. It is likely that the ongoing integration of omics data will transform many aspects of the diagnostic process, including sample acquisition. Additionally, omics data will be integrated into future glioblastoma treatment procedures, with possible applications ranging from identifying potential therapeutic targets to selecting individual treatment plans. The implications of the ongoing integration of omics data for clinical routine, future classification systems, and trial design are also discussed in this review, outlining the pivotal role omics data play in shaping future glioblastoma diagnosis and treatment.]]> Wed, 31 Dec 1969 19:00:00 EST From genes to lifestyle: A multi-dimensional framework for Alzheimer's disease prevention and therapy. Su L, Wang Y
Ageing Res Rev (Jan 2026)

Alzheimer's disease (AD) is a complex neurodegenerative disorder driven by multilayered molecular and cellular mechanisms that cannot be fully elucidated through single-omics approaches. Consequently, large-scale multi-omics integration-encompassing transcriptomics, epigenomics (e.g., methylation), and genetic association studies (GWAS/eQTL/mQTL)-has uncovered critical genetic and epigenetic networks underlying disease risk and progression.Based on these integrative insights, this review emphasized several genes-including KLHL21, SCN2B, ZNF415, and PITRM1-as potential contributors to AD pathogenesis. Notably, single-cell and spatial transcriptomics analyses revealed specific enrichment of these genes in astrocytes, underscoring the pivotal role of this cell type in Aβ clearance, tau propagation, and neuroinflammation. Exercise interventions were shown to selectively modulate the expression of these genes, providing molecular support for the preventive and therapeutic potential of non-pharmacological lifestyle strategies. Drug repurposing analyses using DrugBank have identified promising therapeutic candidates, including FDA-approved agents (e.g., valproic acid, raloxifene, and clomipramine) and naturally derived compounds (e.g., quercetin and fisetin), which may modulate key AD-related pathways. Furthermore, emerging evidence of miRNA-gene regulatory networks suggested an additional layer of post-transcriptional control that may regulate responses to pathological stimuli. Collectively, these integrative insights advocated for a multidimensional precision medicine framework that spans genetic, cellular,network, and lifestyle levels of regulation. This shift from single-target therapeutics to an integrated "gene-cell-network-lifestyle" paradigm open new theoretical and translational avenues for delaying or mitigating AD progression.]]> Wed, 31 Dec 1969 19:00:00 EST Multi-omics approaches to major psychiatric disorders. Oraki Kohshour M, Navarro-Flores A, Heilbronner U, Schulze TG
Neuropsychiatr (Dec 2025)

In recent years, major psychiatric disorders have been intensively researched. Studies have investigated the pathophysiology of these disorders in detail and at various molecular levels with several omics techniques, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics. However, although the results of a single omics study can help shed light on some of the unclear aspects of the biological circuits involved in the pathophysiology of major psychiatric disorders, the complexity of the biological mechanisms underlying these conditions makes it necessary to consider multiple types of omics data and multiple levels of analysis, including various conceptional, methodological, and quality control criteria. Currently, dealing with high-dimensional data and sparse heterogeneous data structures remains one of the biggest challenges to integrating data from multi-omics approaches. The hope is that eventually the development and application of methods to integrate biological and phenotypic data through multi-omics and machine learning-based algorithms may allow early diagnosis of major psychiatric disorders, perhaps even before disease onset, and enable accurate, personalized treatment. In this mini-review, we summarized the main findings of the field by reviewing systematic reviews, meta-analyses, and narrative reviews on the major psychiatric disorders schizophrenia, bipolar disorder, and major depressive disorder.]]> Wed, 31 Dec 1969 19:00:00 EST [Expression of Concern] Gene therapy for human colorectal cancer cell lines with recombinant adenovirus 5 based on loss of the insulin‑like growth factor 2 imprinting. Sun H, Pan Y, He B, Deng Q, Li R, Xu Y, Chen J, Gao T, Ying H, Wang F, Liu X, Wang S
Int J Oncol (Jan 2026)

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, for the immunohistochemical data shown in Fig. 2B and C, the PBS/TUNEL panel in Fig. 2B appeared to be strikingly similar to the PBS/E1A panel shown in Fig. 2C. Furthermore, for the E1A experiments portrayed in Fig. 2C, portions of the data panels shown for the H101 and E1A groups also appeared to be strikingly similar, albeit with rotation of one of the panels. The authors were contacted by the Editorial Office to offer an explanation for this possible anomaly in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Oncology 46: 1759‑1767, 2015; DOI: 10.3892/ijo.2015.2852].]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomics-guided precision oncology: Chromatin variants in prostate tumor evolution. Furlano K, Keshavarzian T, Biernath N, Fendler A, de Santis M, Weischenfeldt J, Lupien M
Int J Cancer (Jan 2026)

Prostate cancer is a common malignancy that in 5%-30% leads to treatment-resistant and highly aggressive disease. Metastasis-potential and treatment-resistance is thought to rely on increased plasticity of the cancer cells-a mechanism whereby cancer cells alter their identity to adapt to changing environments or therapeutic pressures to create cellular heterogeneity. To understand the molecular basis of this plasticity, genomic studies have uncovered genetic variants to capture clonal heterogeneity of primary tumors and metastases. As cellular plasticity is largely driven by non-genetic events, complementary studies in cancer epigenomics are now being conducted to identify chromatin variants. These variants, defined as genomic loci in cancer cells that show changes in chromatin state due to the loss or gain of epigenomic marks, inclusive of histone post-translational modifications, DNA methylation and histone variants, are considered the fundamental units of epigenomic heterogeneity. In prostate cancer chromatin variants hold the promise of guiding the new era of precision oncology. In this review, we explore the role of epigenomic heterogeneity in prostate cancer, focusing on how chromatin variants contribute to tumor evolution and therapy resistance. We therefore discuss their impact on cellular plasticity and stochastic events, highlighting the value of single-cell sequencing and liquid biopsy epigenomic assays to uncover new therapeutic targets and biomarkers. Ultimately, this review aims to support a new era of precision oncology, utilizing insights from epigenomics to improve prostate cancer patient outcomes.]]> Wed, 31 Dec 1969 19:00:00 EST Multiomics Insights into Epigenetic Mechanisms and Their Role as Biomarkers for Acute Coronary Syndrome. D'Agostino A, Rosalinda M, Salvatore M, Monica F
Heart Fail Clin (Jan 2026)

Acute coronary syndrome (ACS) is a complex cardiovascular condition driven by chronic inflammation, immune system imbalances, and epigenetic alterations. Recent research highlights the crucial role of epigenetic modifications in disease progression. Furthermore, differentially methylated regions influence expression in genes associated with immune signaling and cellular functions in ACS patients. ACS is a multifactorial disease driven by complex interactions between genetic, epigenetic, and environmental factors. By leveraging multiomics approaches, clinicians and researchers can uncover novel pathophysiological mechanisms and refine therapeutic strategies for improved cardiovascular outcomes in ACS patients. Integrating multiomics technologies with machine learning-driven analysis is revolutionizing our understanding of ACS.]]> Wed, 31 Dec 1969 19:00:00 EST Regions of Homozygosity Identified with a Chromosomal Microarray in a Korean Population: Distribution, Frequency, and Clinical Interpretation. Kim J, Min S, Seol CA, Seo EJ
Ann Lab Med (Jan 2026)

Single nucleotide polymorphism-based chromosomal microarray analysis (CMA) can detect regions of homozygosity (ROHs), which may be associated with medical conditions; however, limited ROH data, especially in East Asians, complicates clinical interpretations. We characterized ROH distributions and frequencies in a Korean population using CMA, highlighting clinically relevant findings, including suspected uniparental disomy (UPD), using standardized criteria.]]> Wed, 31 Dec 1969 19:00:00 EST From renal development to pathology: An analysis of the multilevel role of insulin‑like growth factor 2 (Review). Sun Y, Hao W, Liu W, Hu W
Mol Med Rep (Jan 2026)

Insulin‑like growth factor 2 (IGF2) is a multifunctional polypeptide hormone that serves important roles in embryonic development, metabolic regulation and disease pathogenesis. IGF2 expression is tightly regulated by genomic imprinting, which restricts transcription to the paternal allele. IGF2 modulates cellular processes, including proliferation, differentiation and metabolic homeostasis, by activating downstream signaling cascades via binding to IGF1 receptor, insulin receptor isoform A and IGF2 receptor. IGF2 is important for kidney development, promoting both nephron formation, and the functional maintenance of renal tubules and glomeruli. Aberrant IGF2 expression is associated with the pathogenesis of diverse renal diseases, including acute kidney injury, chronic kidney disease, diabetic nephropathy, renal cell carcinoma and Wilms' tumor. Under pathological conditions, IGF2 promotes renal fibrosis and promotes tumor expansion and progression by activating key signaling pathways such as the PI3K/Akt and TGF‑β pathways. Due to these roles, IGF2 has attracted growing clinical interest as a potential therapeutic target. The present review presents a comprehensive analysis of the structure and function of IGF2, its roles in renal pathophysiology, and its therapeutic potential, while outlining future research directions.]]> Wed, 31 Dec 1969 19:00:00 EST Omics technologies in mastitis: text mining and topic modelling analysis of global research trends. Esener N
J Dairy Res (Dec 2025)

Mastitis, an inflammation of the mammary gland, is a disease of significant clinical and economic importance. In recent years, advances in omics technologies have provided powerful tools to unravel the complex biological mechanisms underlying mastitis. These approaches encompass diverse fields such as genomics, proteomics, transcriptomics, metagenomics, metabolomics, epigenomics, lipidomics, glycomics, pharmacogenomics, foodomics, interactomics and exposomics. However, despite the rapid growth of omics research, the thematic structure of this literature has not been systematically examined. In this study, latent dirichlet allocation (LDA) was employed to perform topic modelling on publications related to omics and mastitis retrieved from Scopus and Web of Science. The LDA analysis revealed ten distinct topics, labelled according to the most frequent terms within each cluster: 'proteomics', 'pathogen genomics', 'differential expression', 'metabolism', 'genetic selection', 'disease economy', 'molecular diagnostics', 'microbiome', 'antimicrobial resistance' and 'genetic variation.' Among these, the topics of 'genomics', 'differential expression' and 'antimicrobial resistance' accounted for the highest number of publications, while 'metabolism' emerged more recently. All topics exhibited an increasing trend in publication volume over time, likely driven by the declining costs and greater accessibility of high-throughput omics technologies. This study provides a comprehensive thematic overview of omics research on mastitis, identifies key areas of emphasis and emerging directions, and highlights knowledge gaps that may inform future investigations and the development of targeted strategies for disease control and prevention.]]> Wed, 31 Dec 1969 19:00:00 EST Decoding preterm birth: Non-Invasive biomarkers and personalized multi-omics strategies. Farzizadeh N, Najmi Z, Rosenbaum AJ, Amoozgar M, Hariri A, Aminbeidokhti M, Khosravi A, Zarrabi A
Dev Biol (Jan 2026)

A birth that occurs prior to 37 weeks of gestation is referred to as preterm birth (PTB). PTB is a health concern globally with significant outcomes including neonatal morbidity and mortality. Advancements in multi-omics have revolutionized the understanding of PTB pathogenesis, offering new opportunities for early prediction and risk categorization. This review highlights emerging liquid biomarkers derived from proteomic, metabolomic, genomic, transcriptomic, and epigenomic studies, emphasizing the integrative power of multi-omics approaches. Proteomic analyses have revealed key proteins in maternal and fetal compartments associated with inflammatory and extracellular matrix pathways, while metabolomics have identified lipid and metabolite profiles linked to energy metabolism and fetal development. Genomic and epigenomic studies have uncovered genetic variations and microRNAs involved in uterine contractility and immune modulation, providing novel insights into PTB's molecular underpinnings. Transcriptomic research further underscores the act of long non-coding RNAs (ncRNAs) in regulating gene expression and inflammatory responses. Multi-omics integration, coupled with machine learning models, has demonstrated superior predictive accuracy by synthesizing data across these domains, revealing intricate molecular interactions underlying PTB. Future research should prioritize longitudinal multi-omics studies to capture dynamic biological changes during pregnancy, expanding diverse population cohorts to enhance generalizability. Translating multi-omics insights into clinical practice necessitates collaborative efforts to develop cost-effective, accessible biomarker panels and establish standardized guidelines for implementation. These advancements hold the potential to transform prenatal care through personalized risk assessment and targeted preventive strategies, reducing the global burden of PTB.]]> Wed, 31 Dec 1969 19:00:00 EST Exploring Single-Cell and Multi-Omics Technologies and Their Role in Unravelling Tumor Heterogeneity of Hepatocellular Carcinoma. Jyotishi C, Prajapati S, Patel M, Gupta R
J Liver Cancer (Dec 2025)

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Tumor heterogeneity is a major obstacle to effective treatment and is poorly understood using traditional bulk sequencing methods. This review highlights the transformative role of single-cell and multi-omics technologies in determining the cellular and molecular complexities of HCC. We summarize recent advances in single-cell transcriptomics, epigenomics, multi-omics, and spatial transcriptomics platforms, emphasizing their applications in characterizing tumor subclones, cancer-associated fibroblast-immune interactions, circulating tumor cells, and immune-resistant phenotypes. Spatial approaches have revealed the architecture of cancer stem cell niches and tertiary lymphoid structures, providing unprecedented insights into tumor organization and microenvironmental crosstalk. Although still in their early stages, clinical trials have begun to incorporate these technologies, underscoring their translational potential. Single-cell and spatial omics have reshaped HCC research by enabling high-resolution profiling of tumor ecosystems and driving the discovery of biomarkers, therapeutic targets, and strategies for patient stratification. However, high cost, technical expertise, and limited accessibility, particularly in resource-constrained settings, are major barriers to its widespread adoption. Addressing these challenges is critical for translating these powerful approaches into clinical practice and for advancing precision medicine for the treatment of liver cancer.]]> Wed, 31 Dec 1969 19:00:00 EST DNA methylation of genes involved in lipid metabolism drives adiponectin levels and metabolic disease. Sinke L, Delerue T, Wilson R, Lu X, Xia Y, Costeira R, Nasr MK, Beekman M, Franke L, Zhernakova A, Fu J, Gieger C, Herder C, Koenig W, Peters A, Ordovas JM, Dörr M, Grabe HJ, Nauck M, Bell JT, Teumer A, Snieder H, Waldenberger M, Slagboom PE, Heijmans BT
Diabetologia (Jan 2026)

Despite playing critical roles in the pathophysiology of type 2 diabetes and other metabolic disorders, the molecular mechanisms underlying circulating adipokine levels remain poorly understood. By identifying genomic regions involved in the regulation of adipokine levels and adipokine-mediated disease risk, we can improve our understanding of type 2 diabetes pathogenesis and inter-individual differences in metabolic risk.]]> Wed, 31 Dec 1969 19:00:00 EST Hypoxia Rewires Histone Methylation in Glioblastoma Cells via Enzyme Reprogramming Despite Disruption of One-Carbon Metabolism. Tang H, Xu P, Herring J, Zhang K
Biochemistry (Dec 2025)

Hypoxia is a hallmark of the tumor microenvironment that profoundly alters the cellular metabolism and epigenetic regulation. In this study, we investigated how oxygen limitation reprograms histone methylation in glioblastoma cells by integrating stable isotope tracing with high-resolution proteomics and epigenomics. Using deuterium-labeled serine and the RQMID-MS platform, we demonstrated that hypoxia impairs methyl group transfer from serine to histones due to the downregulation of the vitamin B transporter TCN2, which is critical for homocysteine remethylation and SAM synthesis. Despite this blockade in one-carbon metabolism, global histone methylation patterns were not uniformly suppressed. Instead, we observed site-specific changes driven by altered expression of methyltransferases and demethylases, particularly decreased KMT1F (H3K9 methylation) and KMT2B (H3K4 methylation) and increased KDM2A (H3K36 demethylation), KDM3A (H3K9 demethylation), and KMT5A/SETD8 (H4K20 monomethylation). These findings reveal that the histone methylation landscape under hypoxia is governed by a compensatory interplay between one-carbon metabolism and chromatin-modifying enzyme regulation.]]> Wed, 31 Dec 1969 19:00:00 EST Immunofluorescence Staining and Microscopic Imaging of Plant Nuclei for Epigenetic Modifications. Gandhivel VH, Raju S, Shivaprasad PV
Methods Mol Biol (2026)

Histone posttranslational modifications (PTMs) and DNA methylation are the predominant epigenetic modifications on the chromatin that regulate gene expression. These modifications can be spatially resolved using microscopic examination of the nuclei with the help of commercially available antibodies. Here, we describe a detailed method to obtain intact nuclei from plant tissues and reproducibly immunostain the nuclei for specific chromatin marks and microscopic examination. This method can be readily extended to multiple plant species as the antibodies are raised against conserved epigenetic marks.]]> Wed, 31 Dec 1969 19:00:00 EST Single-cell multi-omics characterize colorectal tumors, adjacent healthy tissue and matched (tumor) organoids identifying CRC-unique features. Yu Z, Derksen M, Te Pas BM, Ladstätter S, Overmeer R, Brazda P, van de Wetering M, Pourfarzad F, Vries RGJ, Megchelenbrink W, Bock C, Altucci L, Stunnenberg HG
Int J Cancer (Dec 2025)

Colorectal cancer (CRC) arises in the colorectal tissue driven by genetic disorder or the accumulation of somatic mutations, leading to abnormal epithelial cell growth. In this study, we employed single-nucleus multi-omics analysis, including single-nucleus RNA-seq and single-nucleus ATAC-seq, on over 100,000 high-quality nuclei to investigate the molecular landscape of both primary tissue and patient-derived organoids (PDOs). Our analysis showed that normal PDOs (N-PDOs) derived from tissue adjacent to tumors replicate the cellular composition and differentiation trajectory of colorectal crypts. In contrast, tumor PDOs (T-PDOs) showed patient-specific transcriptomic and epigenomic heterogeneity yet consistently maintained a stem cell-like state. T-PDOs retained the somatic mutation profile of the primary tumor while also exhibiting de novo mutations not detected in either the primary tumor or N-PDOs. Notably, inferred cell-cell interaction analysis highlighted the activin signaling pathway as a potential unique feature of fibroblast-epithelial interactions within the tumor microenvironment. This study provides a comprehensive view of the transition from normal to malignant colorectal epithelium and underscores the utility of PDOs as a faithful model for capturing both conserved and patient-specific features of colorectal cancer.]]> Wed, 31 Dec 1969 19:00:00 EST