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Fructose-1,6-bisphosphate couples glycolytic activity to cell adhesion
Full text linkCellular adhesion to the extracellular matrix is essential for morphogenesis, tissue integrity and survival signalling. The best understood adhesion structures are focal adhesions (FAs). In spite of their importance, our knowledge of upstream factors that integrate FA dynamics with other cellular processes, such as metabolism, remains fragmentary. Using a genome-wide screen, we identify aldolase A, a key glycolytic enzyme that converts fructose-1,6-bisphosphate (FBP), as a regulatory switch that links metabolic flux to FA assembly and cell morphogenesis. We show that cellular FBP serves as a signalling metabolite, which transmits information about the metabolic cell state to the actin-based machinery for cell adhesion and protrusion. This mechanism involves FBP binding to the Rac1 inhibitor RCC2 and a concomitant elevation of Rac1 activity resulting in actin reorganization, increased FA assembly and elevated protrusive activity. Here we predict this mechanism to be crucial for processes ranging from development to cancer
A population approach to cortical GABAergic interneuron function
No full textInhibitory interneuron diversity is a central feature of cortical circuits. The IN-CODE consortium seeks to combine large-scale recordings of interneuron types with machine-learning tools to identify the role of their physiological features, connectivity motifs, and cooperativity in cognitive functions
Integrating UHPLC-MS and MALDI-MSI for spatial nucleoside profiling in FFPE breast cancer: a multimodal molecular pathology framework
No full textFormalin-fixed, paraffin-embedded (FFPE) tissues constitute the primary material for diagnostic pathology and retrospective clinical research, yet their use in metabolomics remains limited due to molecular cross-linking and analyte degradation. Here, we establish a cost-efficient molecular pathology workflow that integrates ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to quantify and spatially map nucleosides in FFPE breast cancer tissues. Optimized extraction using methanol yielded nucleoside profiles comparable to fresh-frozen tissues, while MALDI-MSI enabled the spatial visualization of nine nucleosides across distinct histological regions. Several nucleosides including deoxyadenosine and 5-formylcytosine showed strong discriminatory power between tumor stages, revealing progressive metabolic rewiring during breast cancer progression. Finally, spatial nucleoside patterns observed in a murine model were recapitulated in patientderived FFPE tissues, underscoring the translational potential of nucleoside-based spatial metabolomics for clinical research and biomarker discovery. Together, this workflow establishes MALDI-MSI as a powerful and scalable spatial molecular pathology tool for interrogating nucleoside biology in archival breast cancer samples. Following MALDI-MSI, the same FFPE tissue sections can undergo laser capture microdissection, enabling genomic, proteomic, or targeted metabolomic profiling of MSI-defined tumor niches and microenvironmental regions. This integration directly links spatial nucleoside signatures to molecular alterations relevant to precision oncology in future
STING safeguards epithelial genome integrity and protects from carcinogenesis via mitotic checkpoint control
Full text linkThe cGAS-STING pathway is a central regulator of anti-tumor immunity, sensing cytosolic double-stranded DNA and inducing type I interferon responses. However, whether cGAS-STING directly coordinates DNA damage response in non-immune cells and thereby contributes to cell-intrinsic prevention of oncogenesis is not known. Using mouse models with deletion of ribonucleotide excision repair in the intestinal epithelium (H2b(ΔIEC)) and additional knock-out of STING (H2b(ΔIEC)/STING(-/-), H2b/STING(ΔIEC)) we show that STING deficiency compromises DNA damage induced signalling via ATM and impairs homologous recombination repair, thereby promoting chromosomal instability and driving formation of spontaneous intestinal adenocarcinoma. Mechanistically, STING loss disrupts the NBS1-ATM axis and attenuates DNA damage signalling through enhanced phosphatase-mediated signal termination. Using single strand sequencing, we show that epithelial loss of STING promotes chromosomal instability and accumulation of mutations. By employing kinase screening, we further show that STING deficiency abrogates p53-dependent checkpoint control via overactivation of Cyclin-dependent kinase 1 (CDK1). CDK1 inhibitors lead to a STING-specific sensitization of tumor organoids and colorectal cancer cell lines, pointing towards a STING-specific vulnerability of tumors to CDK1 inhibition. Together, these data identify STING as an epithelial, interferon-independent genome-integrity checkpoint that couples DNA damage signaling to cell-cycle control, thereby restraining chromosomal instability, tumor evolution and revealing a therapeutically exploitable vulnerability in colorectal cancer
Project: PRJEB89341 - Tracing Clonal Hematopoiesis and Lymphoma-Associated Mutations in Hematopoietic Progenitors in B-Cell Non-Hodgkin Lymphoma (B-NHL)
No full textUnlike in leukemia and solid tumors, the role of disease-initiating precursors in B-cell non-Hodgkin lymphomas (B-NHLs) remains underexplored. Such precursors may drive clonal evolution, contributing to the chronic nature of indolent NHLs. Here, we systematically profiled genetic precursor lesions and clonal dynamics using complementary sequencing approaches in a cohort of 43 B-NHLs. Targeted sequencing identified clonal hematopoiesis-associated mutations in the peripheral blood of 55% of patients. Deep sequencing of flow-sorted populations revealed B-cell-skewed propagation, contrasting with findings in individuals without hematologic malignancies. Several mutated clones showed clonal expansion in corresponding tumors, particularly those harboring TP53, EZH2 and TET2 mutations, but not DNMT3A mutant clones. Moreover, we detected lymphoma-associated mutations in hematopoietic progenitor cells (HPCs) in indolent but not aggressive NHLs. Using single-cell genotyping, we provide evidence of mutated HPCs in three follicular lymphoma (FL) cases. Our findings support a pre-neoplastic state in FL pathogenesis, underscoring the potential for novel therapeutic approaches targeting disease-initiating precursors
Indole-3 acetate limits dysbiosis-driven diastolic failure via Hcrt neurons
No full textThis repository contains the data used in the study “Indole-3 Acetate Limits Dysbiosis-Driven Diastolic Failure via Hcrt Neurons” (DOI: 10.1161/CIRCRESAHA.125.326990). Zebrafish gut full-length 16S rDNA amplicon sequencing: Preprocessed 16S rDNA reads from pooled zebrafish larval gut samples. Data include control and ion-dyshomeostasis larvae (IDL). Preprocessing was carried out by Novogene. Zebrafish gut metabolomics W panel: Raw metabolomics files for all samples (control and IDL). Concentrations are given in ng per 75 zebrafish guts. Sample handling and tryptophan measurements were carried out at the Berlin Institute of Health Metabolomics platform. For full experimental steps and data handling details, please see the online supplementary methods in the original article
Stability and individuality of ECG foundation model embeddings in a longitudinal case study
Full text linkPortable ECG devices enable frequent, real-world cardiac monitoring, yet the longitudinal behavior of modern ECG foundation model representations derived from such data remains poorly characterized. In this work, we present a 20-day longitudinal case study examining the temporal stability and individual specificity of ECG representations obtained from a pretrained foundation model applied to consumer-grade six-lead ECG recordings. Daily resting ECGs were collected from two healthy adults using a portable device. For each recording, both latent embedding vectors and task-level probability outputs produced by the model were analyzed. Principal component analysis revealed clear subject-specific clustering in both representation spaces. Temporal drift analysis demonstrated that intra-subject variability remained consistently smaller than inter-subject separation over time. A nearest-centroid distance-margin analysis further showed robust subjectspecific separability without classifier training. Together, these results indicate that ECG foundation model representations derived from portable recordings are stable over time and encode persistent individual characteristics, supporting their potential utility for longitudinal and personalized ECG analysis
OpenDVP: an experimental and computational framework for community-empowered deep visual proteomics
Full text linkDeep visual proteomics (DVP) is an emerging approach for cell type-specific and spatially resolved proteomics. However, its broad adoption has been constrained by the lack of an open-source end-to-end workflow in a community-driven ecosystem. Here, we introduce openDVP, an experimental and computational framework for simplifying and democratizing DVP. OpenDVP integrates open-source software for image analysis, including MCMICRO, QuPath, and Napari, and uses the scverse data formats AnnData and SpatialData for multi-omics integration. It offers two workflows: a fast-track pipeline requiring no image analysis expertise and an artificial intelligence (AI)-powered pipeline with recent algorithms for image pre-processing, segmentation, and spatial analysis. We demonstrate openDVP's versatility in three archival tissue studies, profiling human placenta, early-stage lung cancer, and locally relapsed breast cancer. In each study, our framework provided insights into health and disease states by integrating spatial single-cell phenotypes with exploratory proteomic data. Finally, we introduce deep proteomic profiling of cellular neighborhoods as a scalable approach to accelerate spatial discovery proteomics across biological systems
Resource data for: Rapid UPF1 depletion illuminates the temporal dynamics of the NMD-regulated human transcriptome
No full textResource data for the publication: Rapid UPF1 depletion illuminates the temporal dynamics of the NMD-regulated human transcriptome.
The Resources.zip file contains all intermediate output data needed to reproduce the analyses in the manuscript. The respective code needed to run the analyses can be found in the GitHub repository (https://github.com/boehmv/2025_UPF1_NMDRHT). Please note that the codes require the Resources to be present in the following folder structure:
2025_UPF1_NMDRHT/
├── Resources/ // Contents from the Resources.zip from Zenodo
│ ├── bakR/ // First resource folder
│ └── ... // Other resource folders
├── Plots/ // Output for analyses plots
│ ├── Figure1/ // Plots for Figure1
│ └── ... // Other Plots folders
├── .../ // Other folders from GitHub, e.g. "Analyses" or "Tables"
├── UPF1_NMDRHT_Analysis.R // Top-level R analysis script
└── ... // Other R analysis scripts
The RawData.zip file contains the raw image files from RT-PCR gels and Western blots used in the study. For RT-PCR images, TIF (.tif) and raw Bio-Rad Image Lab Image Document (.scn) files are provided. For Western blots, multi-page TIFs (pages: 1. overlay, 2. raw chemiluminescence, 3. marker image, 4. final) are provided.
Note: the unpacked Resources.zip is over 80 GB in size, please make sure you either have enough space or just extract the relevant data
Phylogenetic analysis of paired breast carcinomas identifies genetic events associated with clonal recurrence and invasive progression
Full text linkDevelopment of ipsilateral breast carcinoma following a diagnosis of breast ductal carcinoma in situ (DCIS) has been assumed to represent recurrence of the primary tumour. However, this may not always be the case, and it is important to determine how often such recurrences represent new tumours. Ipsilateral primary–recurrence pairs (n = 78) were sequenced to test their clonal relatedness. Shared genetic events were identified from whole exome sequencing (n = 54 pairs) using haplotype-specific copy number and phylogenetic analysis. The remaining pairs were sequenced using a targeted panel or low-coverage whole genome sequencing. We included 32 non-recurrent DCIS to compare recurrent and non-recurrent disease. We found that 7% of DCIS recurrences were non-clonal by whole exome sequencing, indicative of a new breast carcinoma. Lower resolution methods detected a higher non-clonality rate (29%). By comparing primary DCIS with their recurrence, we found that the evolution of DCIS to invasive disease was associated with increased ploidy and copy number events. TP53 mutations were enriched in DCIS with clonal recurrence compared with non-recurrent DCIS. Our results verify that de novo ‘recurrent tumours’ of independent origin occur in patients who may be at high risk