This weeks top spatial transcriptomics paper
🧪 Technology & Methods Development
Uncovering spatially resolved functional genomics with CRISPR screen sequencing.
Zhang et al. introduce SPAC-seq, a high-throughput spatial CRISPR screening platform, together with TARDIS, a statistical toolkit to prioritize gene perturbations directly from spatial omics readouts. Applying this framework in tumor models, they connect specific gene knockouts to spatial phenotypes and signaling pathways, including how Icam1 loss in tumor cells drives metastasis via immune suppression and macrophage polarization.
Impact: A powerful platform to link CRISPR perturbations with spatial phenotypes and microenvironmental signaling at scale.
Zhang H et al., https://doi.org/10.1016/j.cell.2026.04.049
A masked generative graph representation learning framework empowering precise spatial domain identification.
Wang et al. develop a masked generative graph representation learning method that combats sparsity in spatial transcriptomics data by jointly modeling spatial and gene expression relationships. The framework yields richer embeddings and enables more accurate identification of spatial domains for downstream analyses.
Impact: An advanced computational approach that boosts spatial domain calling and data usability in sparse ST datasets.
Wang C et al., https://doi.org/10.1093/bioinformatics/btag333
Predicting neoadjuvant breast cancer therapy response using BRIDGE from tumor transcriptomics and histopathology.
Cantore et al. present BRIDGE, an integrative model that combines bulk tumor transcriptomics with histopathology to predict neoadjuvant therapy response in breast cancer. By accounting for intratumoral heterogeneity and coexisting malignant subtypes, BRIDGE aims to refine early treatment decisions in the neoadjuvant setting.
Impact: A multimodal predictive framework that brings molecular decision support closer to routine neoadjuvant breast cancer care.
Cantore T et al., https://doi.org/10.1016/j.annonc.2026.05.700
🧠 Neurobiology
Mapping neuro-vascular unit communications reveals distinct angiogenic programs across developing mouse brain regions.
Bizou et al. combine spatial transcriptomics with region-resolved endothelial single-cell RNA-seq to chart neurovascular unit communication in the postnatal mouse cortex and thalamus. They uncover region-specific angiogenic trajectories and identify neuronal–endothelial TGFβ2–TGFβR1 signaling as a critical regulator of thalamic vascularization, where loss of this pathway induces mTOR-driven vascular malformations that can be rescued pharmacologically.
Impact: A spatially resolved blueprint of neurovascular signaling programs that explains regional vulnerability in developmental brain vascular disorders.
Bizou M et al., https://doi.org/10.1038/s41467-026-73373-w
🫀 Cardiology & Vascular Biology
Integrative Molecular Analyses of Inflammatory and Autoimmune Signals in Cardiac Sarcoidosis.
Neyazi et al. dissect the molecular underpinnings of cardiac sarcoidosis, an inflammatory disease marked by patchy granulomas interspersed with preserved myocardium and fibrotic zones. Through integrative molecular profiling, they explore how inflammatory and autoimmune pathways shape this distinctive histopathology and drive arrhythmias, heart failure, and sudden cardiac death.
Impact: A systems-level view of inflammatory and autoimmune signaling that clarifies mechanisms behind cardiac sarcoidosis progression.
Neyazi M et al., https://doi.org/10.1161/CIRCULATIONAHA.126.079304
Endurance exercise remodels pulmonary vein sleeve myocytes and promotes a proarrhythmic atrial substrate.
Soattin et al. investigate how endurance training alters pulmonary vein (PV) sleeves and the PV–left atrial junction, regions strongly implicated in atrial fibrillation (AF) triggers. They show that chronic exercise remodels these structures toward a proarrhythmic substrate, providing mechanistic insight into the elevated AF risk observed in athletes.
Impact: Mechanistic evidence that endurance exercise reshapes PV myocardial architecture to favor atrial fibrillation initiation.
Soattin L et al., https://doi.org/10.1093/eurheartj/ehag358
Spatial and Single-Cell Mapping Reveals Valvular Interstitial Cell and Macrophage Sex Differences in Calcific Aortic Valve Disease.
Baddour et al. use combined spatial and single-cell mapping to characterize sex-specific cellular programs in calcific aortic valve disease. They uncover distinct fibrocalcific phenotypes in valvular interstitial cells and macrophages between males and females, linking these differences to divergent disease progression toward aortic valve stenosis.
Impact: A spatial single-cell atlas that explains sex-dependent mechanisms driving calcific aortic valve disease.
Baddour T et al., https://doi.org/10.1161/ATVBAHA.126.324694
🧬 Cancer Research
Spatial transcriptomics reveals influence of microenvironment on intrinsic fates in melanoma therapy resistance.
Boe et al. combine spatial transcriptomics with single-cell RNA-seq to delineate intrinsic and microenvironmentally driven resistance programs in melanoma. They identify shared intrinsic resistance states across models and show that, within individual tumors, multiple resistant fates coexist and are differentially selected by local immune and stromal contexts.
Impact: Demonstrates how spatially distinct microenvironments steer melanoma cells into specific resistant fates, informing targeted combination strategies.
Boe RH et al., https://doi.org/10.1186/s13059-026-04112-z
Multi-scale transcriptomic integration reveals LINC00152-high tumor cells promote TGCT progression and T cell exhaustion.
Cao et al. integrate multi-scale transcriptomic data to investigate the role of lncRNAs in testicular germ cell tumors, focusing on LINC00152-high tumor cell populations. They show that these cells drive tumor progression and are associated with T cell exhaustion signatures, positioning LINC00152 as a potential biomarker and therapeutic target.
Impact: Highlights a lncRNA-driven tumor cell state that fuels TGCT progression and immune dysfunction, opening new biomarker and intervention avenues.
Cao J et al., https://doi.org/10.1038/s41416-026-03466-2
🌱 Plant Biology & Spatial Omics
Single-Cell and Spatial Transcriptomics in Plants: From Cell States to Inter-Tissue Coordination.
Phua et al. review how single-cell and spatial transcriptomics are transforming our understanding of plant development and responses by resolving transcriptional states within their native tissue context. Using root hormone signaling, regeneration competence, and immune relay networks as case studies, they outline emerging principles of inter-tissue coordination and propose measurable features for dissecting regulatory interactions across plant tissues.
Impact: A conceptual roadmap for leveraging single-cell and spatial omics to uncover systems-level coordination in plant development and stress responses.
Phua DYZ et al., https://doi.org/10.1093/jxb/erag241