🎗 Cancer Research
Mechanical load inhibits cancer growth in mouse and human hearts.
This study investigates why primary cardiac tumors are rare by showing that mechanical load in the myocardium suppresses cancer cell proliferation in both mouse models and human heart tissues. Using spatial transcriptomics on human cardiac metastases, the authors uncover reduced histone methylation, chromatin compaction, and altered chromatin accessibility at proliferation-related loci, identifying Nesprin-2 as a key mechanosensor.
Impact: Reveals how biomechanical forces and chromatin remodeling protect the heart from cancer, suggesting mechano-based therapeutic strategies.
Ciucci G et al., https://doi.org/10.1126/science.ads9412
Multiomics immune profiling of a patient-relevant orthotopic lung cancer model using SEPARATE-Seq.
The authors develop an injectable orthotopic lung adenocarcinoma model that closely mimics human LUAD and can be cleanly dissected into tumor and adjacent tissues. Combining SEPARATE-Seq with spatial transcriptomics, they map vascular versus intratissue immune compartments, revealing NK cell dysfunction, neutrophil heterogeneity, and spatially restricted immune niches such as lipid-associated TAM rings and interferon-stimulated hubs.
Impact: Provides a spatially resolved, multiomics immune atlas of a highly relevant LUAD model to better predict and test immunotherapies.
Bardet PMR et al., https://doi.org/10.1038/s41467-026-72247-5
AKAP12-LMOD1 signaling defines stromal CAF activation and epithelial junction loss in colorectal cancer.
This work dissects how AKAP12-LMOD1 signaling differentially operates in epithelial versus stromal compartments of colorectal cancer using scRNA-seq, spatial transcriptomics, and multiplex imaging. The authors show that stromal AKAP12-LMOD1 marks ACTA2⁺ cancer-associated fibroblasts linked to fibrosis, gap-junction signaling, and M2-like macrophage polarization, while reduced epithelial AKAP12-LMOD1 associates with loss of tight junction integrity.
Impact: Identifies a compartment-specific stromal program that could be targeted to modulate fibrosis and immunosuppression in stroma-rich colorectal cancer.
Ye QW et al., https://doi.org/10.1038/s41598-026-44680-5
FAP-Targeted LTBR Agonist Drives HEV Differentiation and Immune Niche Formation for Improved Immunotherapy Response in Solid Tumours.
The study evaluates a fibroblast activation protein (FAP)-targeted agonist of lymphotoxin-beta receptor (LTβR) to reprogram the tumor stroma and enhance immune infiltration in solid tumors. By promoting differentiation of high endothelial venules (HEVs) and tertiary lymphoid-like immune niches, the therapy improves responses to immune checkpoint inhibitors in preclinical models.
Impact: Demonstrates a stromal-targeted strategy to engineer intratumoral immune niches and boost checkpoint inhibitor efficacy.
Bianchi R et al., https://doi.org/10.1158/1078-0432.CCR-25-4402
🧠 Neurobiology & Development
Integrating optogenetic fMRI and spatial transcriptomics to reveal circuit-specific gene signatures in fronto- and hippo-thalamic networks.
By combining awake optogenetic fMRI with spatial transcriptomics in the same mice, this study links causal neural circuit activation in fronto- and hippo-thalamic networks to underlying gene expression programs. The authors show that circuit-specific BOLD responses are strongly associated with metabolic and core biochemical pathways, and argue that standard linear models capture only a subset of these gene–process relationships.
Impact: Establishes a powerful multi-omics framework to mechanistically connect transcriptomic architecture with large-scale brain network function.
Zhang C et al., https://doi.org/10.1038/s41467-026-71923-w
Retinoic acid drives cell fate specification, maturation and retinal regionality in human retinal organoids.
Using human retinal organoids, the authors systematically vary retinoic acid timing and dosage to dissect its role in retinal cell fate decisions, maturation, and spatial patterning. Single-cell and spatial transcriptomics show that low RA levels bias toward a macula-like identity, whereas high RA skews development toward peripheral-like retina, with distinct effects on photoreceptors and interneurons.
Impact: Offers a tunable RA-based strategy to engineer region-specific human retinal organoids for disease modeling and regenerative therapies.
Lim BY et al., https://doi.org/10.1038/s41467-026-72130-3
🧬 Technology & Methods Development
Subcellular mRNA localization patterns across tissues resolved with spatial transcriptomics.
This study applies high-resolution spatial transcriptomics across multiple mammalian tissues to systematically map subcellular mRNA localization, including nuclear retention and apical–basal polarity in epithelia. A new computational framework leverages image-derived features to quantify transcript localization, revealing conserved and tissue-specific intracellular RNA distribution signatures in gastrointestinal and liver epithelia.
Impact: Extends spatial transcriptomics into the subcellular domain, enabling routine, high-throughput analysis of intracellular RNA localization in health and disease.
Novoselsky R et al., https://doi.org/10.1038/s41467-026-72156-7
Reference-free discovery with barcoded single-cell sequencing.
The authors present sc-SPLASH, a statistics-first, reference-free pipeline for barcoded single-cell and spatial transcriptomics data that goes beyond standard alignment and differential expression. Its BKC preprocessing module is ~50× faster than UMI-tools, and the framework uncovers biologically relevant, previously unannotated secreted repeat proteins in sponge and tunicate immune-like cells.
Impact: Delivers a fast, reference-free discovery engine that unlocks hidden transcriptomic variation in single-cell and spatial datasets, especially in non-model organisms.
Dehghannasiri R et al., https://doi.org/10.1038/s41587-026-03084-6
🛡 Immunology & Autoimmunity
A spatially coordinated keratinocyte-fibroblast circuit recruits MMP9⁺ myeloid cells to drive type I interferon-driven inflammation in photosensitive autoimmunity.
This work integrates single-cell RNA-seq, spatial transcriptomics, proteomics, UVB provocation, and in vitro models to dissect photosensitivity in cutaneous lupus and dermatomyositis. The authors identify a keratinocyte–fibroblast signaling circuit that recruits MMP9⁺CD14⁺ myeloid cells producing IFNβ, and demonstrate in a proof-of-concept trial that anti–type I interferon therapy blocks UVB-induced myeloid infiltration and reduces photosensitivity.
Impact: Pinpoints a spatially organized inflammatory circuit and cellular target that can be therapeutically exploited in photosensitive autoimmune skin disease.
Wang Y et al., https://doi.org/10.1038/s41590-026-02502-w
🩺 Liver & Metabolic Disease
Spatial profiling of chronic liver disease: a pilot spatial case series.
In this pilot study, sequencing-based spatial transcriptomics is applied to chronic liver disease tissues including alcohol-associated liver disease, MASH, and chronic hepatitis C using a viral-aware workflow. The analyses reveal shared pseudolobular functional architectures with etiology-specific overlays of immune, metabolic, and antiviral programs, including spatially confined viral RNA and immune-mesenchymal signaling hubs.
Impact: Provides an initial spatial blueprint of chronic liver disease architecture that links histology with local immune, fibrotic, and viral-response niches.
Sasagawa S et al., https://doi.org/10.1038/s41598-026-49400-7