bims-gerecp Biomed News
on Gene regulatory networks of epithelial cell plasticity
Issue of 2026–08–16
nine papers selected by
Xiao Qin, University of Oxford
  1. Epigenetic modulation of stromal cell states underpins pathological tissue niches in Crohn's disease.
  2. A categorization of spatial transcriptomics methods for cell-cell communication analysis.
  3. Simultaneous single-cell profiling of chromatin, transcriptome and surface markers with OneCell CUT&Tag captures epigenomic reprogramming.
  4. Patient-Derived Organoids in Gastrointestinal Disease: Current Applications, Limitations, and Future Perspectives.
  5. From pixels to patterns: the AI revolution in stem cell-derived models.
  6. Beyond the biopsy: the new era of non-invasive staging and biomarkers in colorectal cancer.
  7. Function-First Organoid Engineering for Regenerative Medicine: Current Challenges and Future Perspectives.
  8. Histological aging signatures for monitoring tissue-specific aging and disease.
  9. STAT3 signaling inhibitors for cancer treatment.
  1. Nat Immunol. 2026 Aug 12.
    Epigenetic modulation of stromal cell states underpins pathological tissue niches in Crohn's disease.
    Simon Koplev, Osheen Sharma, Simon Woelfel, Ni Huang, Mathilde Pohin, Adrian Feile, Maria Warschinke, Mikel Rezola Artero, Sharujan Suthakaran, Ioannis Sarropoulos, J Patrick Pett, Julia Nyman, Tom Thomas, Duy Pham, Bin Li, Moustafa Attar, Julia Pakpoor, Kate Milosevic-Hutton, Alistair Easton, Matt Butler, James Dunford, Martin Philpott, Mark Coles, Christopher D Buckley, Calliope Dendrou, Khalid Shamiyah, Lorenz Kretschmer, Lisa Dratva, Fadi Issa, Joanna Hester, Jens Rittscher, Alissa Walsh, Simon P Travis, Fränze Progatzky, Lukas W Unger, Mark Bignell, Katherine Baker, Bruce George, Hussein Al-Mossawi, Paul Klenerman, Alexander S Mosig, Udo Oppermann, Sarah A Teichmann, Fiona M Powrie, Matthias Friedrich.
      Stromal cell states are altered in active Crohn's disease (CD), but their origin and phenotypic stability are unknown. Using single-cell spatial transcriptomics, RNA sequencing and ATAC sequencing of ~2,500,000 cells, we map 18 distinct stromal cell states within their cellular and cytokine signaling environments in human full-thickness CD bowel. Inflammatory fibroblasts (IFs) reside in immune cell-rich mucosal ulcers and are induced through combinatorial cytokine exposure suppressing submucosal universal fibroblast programs. The IF state is stabilized through transcription factor (TF) activity of GLI3, TWIST1, ETV4, PRDM1 and RELB, and does not spontaneously revert; however, histone deacetylase inhibition destabilizes the IF state, preventing IF secretome-induced epithelial transmigration and activation of neutrophils. The IF open chromatin configuration is distinct from that of fibrotic contractile stroma, which populate adjoining immune-depleted submucosal fibrotic niches. These findings show that microenvironments in pathological tissue niches shape open chromatin configuration of stromal states that are amenable to modulation by epigenetic modifiers.
    DOI:  https://doi.org/10.1038/s41590-026-02617-0
  2. Trends Genet. 2026 Aug 14. pii: S0168-9525(26)00173-3. [Epub ahead of print]
    A categorization of spatial transcriptomics methods for cell-cell communication analysis.
    Zlatka Fischer, Katharina Imkeller, Marcel H Schulz, Nina Baumgarten.
      Cell-cell communication (CCC) is involved in regulating cellular behavior in tissues. Spatial transcriptomics adds local context to gene expression, enabling more biologically grounded CCC inference than single-cell RNA-seq alone. Rapid method development has yielded diverse CCC methods, each addressing distinct biological questions through varied analytical frameworks. We review 33 recent methods and organize them into three categories: inference of communication networks at cell-type or single-cell resolution, modeling of microenvironment-driven transcriptional variability and regulatory modules, and estimation of spatially informed signaling gene co-associations and higher-order interaction structures. We offer a structured guide for method selection aligned with researchers' analytical goals, highlighting strengths, limitations, and key technical features to support the informed application of CCC inference methods in spatial transcriptomic research.
    Keywords:  cell–cell communication; computational tools; spatial transcriptomics
    DOI:  https://doi.org/10.1016/j.tig.2026.07.004
  3. Nat Biotechnol. 2026 Aug 12.
    Simultaneous single-cell profiling of chromatin, transcriptome and surface markers with OneCell CUT&Tag captures epigenomic reprogramming.
    Anna Schwager, Eve Moutaux, Adeline Durand, Alexandra Van Keymeulen, Amélie Viaene, Mélanie Miranda, Louisa Hadj Abed, Simon Besson-Girard, Marion Lambault, Délia Dupré, Grégoire Jouault, Melissa Saichi, Juliette Bertorello, Simon Dumas, Mathias Schwartz, Marthe Laisné, Justine Marsolier, Manuel Guthmann, Lorraine Bonneville, Urvashi Chitnavis, Déborah Bourc'his, Elisabetta Marangoni, Nicolas Servant, Cédric Blanpain, Leïla Perié, Céline Vallot.
      Simultaneous mapping of chromatin states and transcriptomes in rare cell populations is challenging, as most methods require thousands of cells and are limited in their ability to capture multiple molecular layers accurately within the same cell. Here we introduce OneCell CUT&Tag, a method that provides matched high-resolution epigenome, full-transcriptome and surface marker quantification from every cell, with input as low as one cell, without relying on computational aggregation into metacells. Using this approach, we uncover epigenomic priming of basal cells in the mammary gland and capture the dynamics of basal-to-luminal transdifferentiation, suggesting that epigenomic and transcriptional remodeling do not occur in complete synchrony during cell-fate conversion. Adaptable to diverse samples and tissues, this method also reveals the role of H3K27me3 in shaping zygotic expression programs. By matching multiple layers of molecular information within individual cells, OneCell CUT&Tag reveals how complementary regulatory layers shape cellular identity and state, enabling the study of rare biological samples in development and disease.
    DOI:  https://doi.org/10.1038/s41587-026-03259-1
  4. Int J Mol Sci. 2026 Aug 02. pii: 6949. [Epub ahead of print]27(15):
    Patient-Derived Organoids in Gastrointestinal Disease: Current Applications, Limitations, and Future Perspectives.
    Amanda Caruso, Yasmine Hamrouni, Antonella Delvecchio, Riccardo Memeo, Stefano Martinotti.
      The development of patient-derived organoids (PDOs) has substantially advanced the study of gastrointestinal diseases by providing three-dimensional human models that faithfully recapitulate the structural, molecular, and functional characteristics of native tissues. Unlike conventional two-dimensional cultures and animal models, intestinal organoids preserve epithelial architecture, cellular heterogeneity, and patient-specific genetic features, enabling more physiologically relevant investigations of gastrointestinal physiology and disease. Recent technological advances, including co-culture systems, organoid-derived monolayers, and organ-on-chip platforms, have further expanded their ability to model epithelial interactions with immune cells, stromal components, and the gut microbiota. These developments have facilitated mechanistic studies of epithelial barrier function, host-microbiota communication, microbial metabolites, and endocrine signaling, while also supporting translational applications in inflammatory bowel disease, infectious disorders, inherited gastrointestinal diseases, and gastrointestinal cancers. Moreover, patient-derived organoids have emerged as promising platforms for drug screening, biomarker discovery, precision medicine, and regenerative therapies. Despite these advances, several challenges remain, including limited representation of the native tissue microenvironment, lack of standardized culture protocols, scalability, and regulatory issues that currently restrict routine clinical implementation. This review summarizes recent progress in gastrointestinal organoid technology, highlighting current applications, emerging experimental platforms, and future perspectives for integrating organoid-based models into translational research and personalized medicine.
    Keywords:  3D cell culture; gastrointestinal diseases; organoid-on-chip; patient-derived organoids; precision medicine
    DOI:  https://doi.org/10.3390/ijms27156949
  5. Nat Methods. 2026 Aug 14.
    From pixels to patterns: the AI revolution in stem cell-derived models.
    Luca Deininger, Paolo Caldarelli, Magdalena Zernicka-Goetz, Ralf Mikut.
      Artificial intelligence (AI) is rapidly transforming stem cell and developmental biology, offering new strategies to analyze, interpret and optimize complex, dynamic systems such as organoids and stem cell-derived embryo models. In this Perspective, we chart the integration of AI into image-based analysis of stem cell systems, highlighting how deep learning, convolutional neural networks and emerging foundation models enable automated classification, segmentation and phenotyping at increasing scale and precision. We showcase applications in phenotyping, drug screening and mechanistic discovery, including real-time fate prediction and the identification of hidden morphological signatures linked to differentiation and disease. Practical challenges, including limited annotated data, model interpretability and live imaging constraints, are examined alongside future opportunities, such as multimodal integration, real-time experimental steering and protocol optimization. Altogether, we argue that AI is not merely an analytical tool, but a discovery engine that enhances reproducibility, accelerates insight and brings us closer to a mechanistic understanding of self-organization in complex stem cell-derived systems.
    DOI:  https://doi.org/10.1038/s41592-026-03202-x
  6. Clin Transl Oncol. 2026 Aug 08.
    Beyond the biopsy: the new era of non-invasive staging and biomarkers in colorectal cancer.
    Nahlah Al Srouji, Abdulrahman Ismaiel, Aida Puia, Mohamed Ismaiel, Mohamed Abosheisha, Stefan-Lucian Popa, Ion Cosmin Puia.
      Colorectal cancer (CRC) management is increasingly challenged by shifting demographics, notably the rise in aggressive early-onset CRC, and the limitations of conventional anatomical staging. This comprehensive review explores the paradigm shift toward noninvasive and minimally invasive pre-operative biomarkers for CRC diagnosis, staging, and prognostic stratification. While traditional colonoscopy and radiological imaging often fail to capture intratumoral heterogeneity and micrometastatic dissemination, emerging biomarker modalities offer real-time, high-fidelity tumor phenotyping. Advanced fecal tests and microbiome profiling, highlighting enriched taxa like Fusobacterium nucleatum, provide crucial insights into the tumor microenvironment, disease progression, and localized immune evasion. Concurrently, accessible systemic immune-inflammatory scores, such as the pan-immune-inflammation value (PIV), systemic immune-inflammation index (SII), and the cancer-specific Glasgow prognostic score (C-GPS), demonstrate robust capabilities in predicting overall survival, disease recurrence, and pathological complete response. The clinical maturation of circulating tumor DNA (ctDNA) represents a cornerstone of this evolution, offering unparalleled sensitivity for detecting molecular residual disease (MRD) post-surgery and dynamically guiding adjuvant chemotherapy de-escalation or escalation protocols. Ultimately, the future of CRC precision oncology relies on multimodal convergence, synergistically integrating liquid biopsies, radiomics, and clinical scores into unified predictive models or "Digital Twins". Emphasizing the need for multi-center standardization and prospective validation, this integrated noninvasive biomarker landscape promises to overcome current diagnostic blind spots, optimize therapeutic interventions, and fundamentally individualize patient care.
    Keywords:  Cancer-specific Glasgow prognostic score; Colorectal cancer; Pan-immune-inflammation value; Prognostic biomarkers; Systemic immune-inflammation index
    DOI:  https://doi.org/10.1007/s12094-026-04531-1
  7. Stem Cells. 2026 Aug 08. pii: sxag044. [Epub ahead of print]
    Function-First Organoid Engineering for Regenerative Medicine: Current Challenges and Future Perspectives.
    Yusuke Nishimura.
      Organoid technology has emerged as a powerful platform for modeling human development, disease, and drug responses. Advances in stem cell biology and bioengineering have enabled the generation of increasingly sophisticated organoid systems that recapitulate key structural and cellular features of native tissues. However, despite substantial progress, the translational impact of organoids in regenerative medicine remains limited. Greater structural complexity and anatomical resemblance have not consistently translated into sustained therapeutic function or clinical applicability. Major barriers include incomplete maturation, inadequate vascular and immune integration, limited long-term functional stability, and challenges in reproducibility and scalability. These limitations reflect a conceptual mismatch between structure-driven organoid development and the functional requirements of regenerative medicine. Here, we propose a function-first framework in which regenerative organoids are engineered and evaluated according to measurable therapeutic outcomes, including tissue-specific function, vascular integration, immune compatibility, reproducibility, scalability, and long-term stability. We further discuss emerging bioengineering strategies, including vascularization, immune incorporation, organ-on-a-chip platforms, advanced biomaterials, and automated manufacturing, that may accelerate clinical translation. Reframing organoids as functionally engineered therapeutic platforms rather than increasingly complex anatomical models provides a conceptual foundation for advancing regenerative organoid therapies.
    Keywords:  Bioengineering; Organoid; Regenerative medicine; Self-organization; Stem cells
    DOI:  https://doi.org/10.1093/stmcls/sxag044
  8. Nat Med. 2026 Aug 14.
    Histological aging signatures for monitoring tissue-specific aging and disease.
    Ernesto Abila, Iva Buljan, Yimin Zheng, Lisa Kleissl, Sigrid Klotz, Tamas Veres, Zhilong Weng, Maja Nackenhorst, Rizqah Kamies, Anja Michl, Safwen Kadri, Samir Moustafa, Wolfgang Hulla, Matthias Perkonigg, Mathias Drach, Philipp Tschandl, Barbara Sterniczky, Matthias Heinig, Laurens J De Sadeleer, Wim Wuyts, Bart Vanaudenaerde, Laurens J Ceulemans, Daniel D Buchanan, Lochlan J Fennell, Georg Stary, Yuri Tolkach, Adelheid Wöhrer, Herbert B Schiller, André F Rendeiro.
      Aging is the primary risk factor for chronic disease and is characterized by profound structural and architectural remodeling of human tissues. Here, we present a comprehensive assessment of these changes using 25,712 whole-slide histopathological images from 40 tissue types across 983 individuals in the Genotype-Tissue Expression cohort. By leveraging deep learning, we quantified nuanced morphological alterations to develop 'tissue clocks', predictors of biological age that reflect tissue structural integrity and physiological fitness. These clocks correlate with established aging markers, such as telomere attrition, subclinical pathologies and comorbidities. Through a systematic evaluation of biological aging rates across organs, we identified associations of tissue-specific age acceleration with demographic, lifestyle and medical factors, highlighting potentially modifiable risk factors that affect tissue aging. Furthermore, by integrating paired histology and transcriptomic data, we developed a strategy to predict tissue-specific age gaps directly from blood samples. We validated this approach by identifying disease-relevant organ aging across independent cohorts for eight prevalent diseases, including Alzheimer's disease, stroke and Crohn's disease. This work positions tissue architecture as a critical integrator of molecular and cellular changes over the course of aging, demonstrates that histopathological imaging provides a robust framework for monitoring tissue-specific aging and offers a scalable foundation for understanding organ-level physiological decline in health and disease.
    DOI:  https://doi.org/10.1038/s41591-026-04566-5
  9. Trends Pharmacol Sci. 2026 Aug 08. pii: S0165-6147(26)00173-2. [Epub ahead of print]
    STAT3 signaling inhibitors for cancer treatment.
    Rasaq Akinsola, Jing Xian, James Turkson.
      Pharmacological targeting of Signal Transducer and Activator of Transcription 3 (STAT3) in cancer has demonstrable antitumor efficacy. However, suitably potent, efficacious, and safe STAT3 inhibitors are scarce, and only a handful have entered clinical trials, limiting our knowledge of the extent of clinical benefit. Outcomes of recently completed trials in advanced cancers range from improved overall survival and complete responses in a cohort of patients with phosphotyrosine STAT3 positivity to partial responses and progressive disease in unselected patients. Advancements in oligonucleotide technologies and the integration of E3 ligase-specific proteolysis-targeting chimeras and molecular glue protein degrader strategies are accelerating the transition of STAT3 inhibitors into clinical testing. This review examines recent STAT3-targeted modalities and their preclinical and clinical activities. It concludes by underscoring the value of biomarker-informed approaches to optimize patient outcomes, combination therapies to improve clinical benefits, and artificial intelligence/machine learning tools to accelerate development.
    Keywords:  STAT3; antitumor efficacy; cancer; drug discovery; inhibitory modalities; therapy
    DOI:  https://doi.org/10.1016/j.tips.2026.07.004
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