🧫 Cancer Research & Tumor Microenvironment
Oncogenic function and transcriptional dynamics of MYCN in liver tumorigenesis.
This study demonstrates that MYCN overexpression cooperates with AKT activation to drive liver tumorigenesis, producing tumors that mirror stress-adaptive human HCC subtypes. Time-resolved spatial transcriptomics reveal a MYCN-enriched niche marked by EMT and Wnt/β-catenin signaling that expands during progression and sits adjacent to malignant cells. A machine learning–derived MYCN niche score predicts recurrence and identifies EMT-prone, precancerous microenvironments in non-tumor liver.
Impact: Establishes MYCN as both a functional driver and spatial biomarker of tumor-promoting niches, enabling transcriptomic risk stratification from non-tumor liver tissue.
Qin XY et al., https://doi.org/10.1073/pnas.2521923123
In Silico Reconstruction of Primary and Metastatic Tumor Architecture using Geographic Information System-Augmented Spatial Transcriptomics.
The authors introduce GIS-ROTA, a GIS-augmented framework that overlays pathway and cell type enrichment with spatial autocorrelation to define functionally meaningful tumor domains. Applied to Visium data from primary and metastatic ER+ breast tumors, GIS-ROTA reveals co-localization of estrogen response with metabolic programs and mutual exclusivity with metastasis- and immune-related pathways. This biologically informed approach avoids purely cluster-driven interpretations and directly links spatial patterns to tumor behavior.
Impact: Provides a functionally grounded spatial analytics framework to map actionable biological niches in primary and metastatic tumors.
Yoo JY et al., https://doi.org/10.1158/0008-5472.CAN-25-3161
INHBA: a mitochondrial-related pan-cell death gene associated with the prognosis and immunity of OSCC.
By integrating TCGA, multiple GEO datasets, and mitochondrial gene catalogs with nine machine learning approaches, this work identifies INHBA as the most prognostic mitochondria-associated pan-cell death gene in oral squamous cell carcinoma. Single-cell and spatial transcriptomics show INHBA is highly expressed in myofibroblastic CAFs and tightly colocalizes with CAF-rich regions, linking it to immunomodulation and poor outcome. Drug sensitivity analysis highlights selumetinib and naltrexone as potential therapies for INHBA-high tumors.
Impact: Pinpoints INHBA as a spatially localized stromal target and prognostic biomarker in OSCC, nominating drug candidates for INHBA-driven disease.
Zhang X et al., https://doi.org/10.1038/s41598-026-38131-4
SPP1(+) Macrophage-POSTN(+) Fibroblast-Endothelial Triad Dictates Immunotherapy Response in Bladder Cancer.
Using integrated spatial transcriptomics, single-cell RNA-seq, and multiplexed immunofluorescence, this study dissects tumor microenvironmental structures associated with anti–PD-1 response in bladder cancer. Non-responders harbor an accumulation of MYBL2-high stem-like malignant epithelial cells at tumor boundaries and a distinct triad of SPP1+ macrophages, POSTN+ fibroblasts, and endothelial cells. These spatially organized niches appear to shape immune exclusion and resistance to checkpoint blockade.
Impact: Identifies a discrete spatial immune–stromal–vascular triad and stem-like tumor front that can serve as biomarkers and targets for improving immunotherapy in bladder cancer.
Chen H et al., https://doi.org/10.1096/fj.202504456RR
🫀 Cardiovascular & Metabolic Disease
Atherosclerotic Fibrous Plaques in Women Present ECM Remodeling Linked to TGF-β.
This study investigates sex-specific molecular programs in fibrous atherosclerotic plaques, which are more common in women and linked to plaque erosion. The authors focus on extracellular matrix remodeling and its association with TGF-β signaling as a potential driver of these sex-dependent histologic features. The work aims to connect plaque architecture with distinct molecular pathways that may underlie women’s higher burden of erosion-related acute coronary syndromes.
Impact: Highlights TGF-β–driven ECM remodeling as a candidate pathway explaining sex-specific vulnerability in fibrous atherosclerotic plaques.
Sakkers TR et al., https://doi.org/10.1161/CIRCRESAHA.125.327624
BMAL1 insufficiency increases the risk of thoracic aortic aneurysm and dissection.
Focusing on thoracic aortic aneurysm and dissection, this study links reduced BMAL1 activity to enhanced apoptosis of vascular smooth muscle cells. The authors dissect how circadian clock disruption exacerbates vessel wall degeneration, thereby increasing susceptibility to catastrophic aortic events. Molecular analyses suggest BMAL1 as a nodal regulator of survival pathways in aortic smooth muscle.
Impact: Connects circadian dysregulation via BMAL1 insufficiency to structural aortic failure, nominating clock pathways as potential therapeutic targets in TAAD.
Song W et al., https://doi.org/10.1093/cvr/cvaf259
🧠 Neurobiology & Developmental Biology
Distinct spatial patterning and transcriptomic landscapes of human neural organoids by localized delivery of morphogens.
This work presents a Matrigel-free passive diffusion-based morphogen gradient generator (PdMG) that creates stable, steep morphogen gradients across human neural organoids. By applying SHH/WNT inhibitor, WNT, or retinoic acid gradients, the authors generate organoids patterned along dorsal–ventral and rostro–caudal brain axes, validated by spatial transcriptomics. The patterned organoids display robust regionalization, active neurogenesis, and GABAergic interneuron migration, modeling key aspects of human brain development.
Impact: Establishes a versatile spatial morphogen platform plus spatial transcriptomics to precisely engineer and read out human brain regionalization in organoids.
Yang F et al., https://doi.org/10.1016/j.stem.2026.01.008
🐛 Invertebrate & Developmental Biology
Single-cell and spatial transcriptomics define 20E-driven developmental reprogramming in silkworm wing disc.
Combining single-nucleus RNA-seq across 10 timepoints with spatial transcriptomics, this study builds a spatiotemporal atlas of silkworm wing disc development. The authors identify wing morphogenesis (Wm) cells as central progenitors that orchestrate lineage decisions via hierarchical transcriptional reprogramming and hormone-responsive signaling modules. Treatment with 20-hydroxyecdysone rapidly accelerates fate transitions and gene expression, supporting a five-stage Gene Transition Model of hormone-driven organogenesis.
Impact: Delivers a high-resolution spatial and temporal blueprint of hormone-controlled wing development, informing broader principles of insect organogenesis and agricultural manipulation.
Liu Q et al., https://doi.org/10.1038/s41467-026-69518-6
🌿 Plant Biology & Systems Development
Integrating scRNA-seq and snRNA-seq with spatial transcriptomics to unlock the xylem puzzle.
This paper integrates scRNA-seq, snRNA-seq, and spatial transcriptomics to capture the full continuum of xylem differentiation, including late-stage cells excluded by protoplast-based methods. The approach reconstructs trajectories from early xylem progenitors through secondary cell wall deposition to programmed cell death, while mapping these states back into intact tissue context. The resulting atlas resolves cell-type-specific gene programs underlying secondary growth and biomass accumulation in woody plants.
Impact: Provides a comprehensive multi-modal spatial framework to decode xylem development, advancing fundamental plant biology and biomass engineering.
Wei M et al., https://doi.org/10.1186/s13059-026-04007-z
🦠 Immunology & Inflammatory Disease
Single-cell and spatial transcriptomics unveil myeloid-lymphoid crosstalk and the dermal immune niche underlying palmoplantar pustulosis.
Using single-cell and spatial transcriptomics, this study characterizes the dermal immune landscape in palmoplantar pustulosis, a chronic inflammatory skin disease of palms and soles. The authors delineate myeloid and lymphoid populations and map their spatial interactions, revealing a specialized dermal immune niche that likely sustains pustular inflammation. These data uncover candidate molecular circuits and cell–cell communication pathways driving disease chronicity.
Impact: Defines a spatially organized dermal immune niche and myeloid–lymphoid crosstalk in PPP, suggesting new cellular and molecular targets for intervention.
Lee H et al., https://doi.org/10.1016/j.jaci.2026.01.028