🛡️ Immunology & Cancer Immunotherapy
Dendritic cells control tertiary lymphoid structure development and maintenance in cancer.
Using spatial transcriptomics and multiplex imaging across human tumors, this study uncovers how CCR7⁺ dendritic cells orchestrate the formation and maintenance of tertiary lymphoid structures (TLSs), key niches associated with better immunotherapy response. The work dissects spatial organization and cellular crosstalk within TLSs, linking dendritic cell positioning and phenotype to local antitumor immunity.
Impact: Provides mechanistic insight into how dendritic cells shape TLS biology, opening routes to rationally boost immunotherapy responses via spatially targeted immune modulation.
Mattiuz R et al., https://doi.org/10.1126/science.ady1678
Quantitative calibration of a spatial QSP model identifies fibroblast impact on HCC immunotherapy.
By integrating spatial transcriptomics with a mechanistic spatial QSP (spQSP) model of liver cancer, the authors quantitatively calibrate tumor architecture and simulate how fibroblasts shape the immunosuppressive microenvironment. The calibrated model recapitulates fibroblast-driven T cell exclusion, predicts spatial tumor states after combination immunotherapy, and proposes spatial and non-spatial biomarkers of response.
Impact: Demonstrates how spatial omics can powerfully inform predictive in silico models for personalized cancer immunotherapy and fibroblast-targeted interventions.
Zhang S et al., https://doi.org/10.1073/pnas.2525799123
🧬 Technology & Methods Development
Whole-transcriptome-scale isoform-resolved spatial imaging of single cells in tissues.
This work introduces an in situ RNA amplification strategy coupled with MERFISH to achieve isoform-resolved, whole-transcriptome spatial transcriptomics in intact tissues. Imaging ~33,000 RNA species (including ~10,000 isoforms) in mouse brain, the approach reveals region- and cell-type-specific isoform usage and cell–cell communication programs that were previously inaccessible.
Impact: Establishes a next-generation spatial platform that brings isoform-level resolution to whole-transcriptome imaging, enabling far richer molecular dissection of tissue organization.
Cohen L et al., https://doi.org/10.1016/j.cell.2026.06.027
🧠 Neurobiology & Sensory Systems
Morphological and functional diversity of spatially resolved vestibular ganglion neuron cell types.
Combining single-cell and spatial transcriptomics, this study defines five transcriptionally and spatially distinct vestibular ganglion neuron types with unique innervation patterns, target zones, and synaptic morphologies. Genetic labeling and functional assays link one specific neuron type to gravity sensing and otolith-dependent vestibulo-ocular reflexes, providing a cell-type-resolved map of vestibular computations.
Impact: Delivers a spatially grounded cell-type atlas of vestibular neurons that mechanistically connects molecular identity to balance and eye-movement control.
Liu R et al., https://doi.org/10.1073/pnas.2530677123
Sensory nerve-derived signaling coordinates oropharyngeal structural organization that supports suckling and vocalization in neonatal mice.
Using single-cell and spatial transcriptomics, the authors show that trigeminal sensory neurons secrete GDF11 to pattern soft palate musculature via cranial neural crest-derived perimysial cells and an Akt–FoxO1–Thbs3 signaling axis. Loss of sensory neuron Gdf11 disrupts muscle architecture, impairs suckling and vocalization, and these defects can be partially rescued by pharmacological AKT activation.
Impact: Reveals a nerve-derived trophic program that spatially coordinates neuromuscular development, suggesting therapeutic entry points for congenital oropharyngeal disorders.
Cha S et al., https://doi.org/10.1038/s41467-026-74959-0
Reduced melanocortin tone modulates feeding during pregnancy in mice.
This study demonstrates that pregnancy activates AgRP neurons and suppresses POMC neurons in the arcuate nucleus, changes that are acutely required to drive gestational hyperphagia. Single-cell resolution spatial transcriptomics maps pregnancy-induced transcriptional remodeling across arcuate neuron populations, highlighting broad rewiring of energy homeostasis circuits.
Impact: Connects pregnancy-associated changes in feeding behavior to spatially resolved hypothalamic circuit and transcriptional adaptations.
Possa-Paranhos IC et al., https://doi.org/10.1038/s41467-026-75650-0
🧠 Neurobiology & Brain Aging
Cellular hallmarks and aging clock of the human lung parenchyma.
(Despite its title focus on lung, this is a systems-level neuro-immune–relevant aging study leveraging spatial platforms.) By integrating single-cell and spatial transcriptomics from large human lung cohorts, the authors chart cell type–specific aging signatures, including reduced alveolar stemness, macrophage depletion with mitochondrial stress, and expansion of pro-inflammatory, exhausted T cells. Machine learning models trained on these data predict biological lung age and identify candidate biomarkers of age-linked disease risk.
Impact: Provides a spatially resolved, cell-type-resolved atlas of lung aging and an interpretable aging clock with implications for age-related respiratory and immune pathologies.
Xu K et al., https://doi.org/10.1038/s41467-026-75427-5
🧪 Developmental Biology
Spatial transcriptomic mapping of postnatal mouse uterine development.
Using high-resolution in situ spatial transcriptomics integrated with histology, proteomics, and genetics, this study maps uterine development from postnatal day 3 to 21 at cellular and signaling-pathway resolution. The work reveals that endometrial glands emerge from luminal epithelium via progressive transcriptional reprogramming and delineates spatially compartmentalized Wnt, retinoic acid, Hedgehog, RTK, Notch, TGFβ, BMP, Hippo, and PI3K–mTOR signaling during adenogenesis.
Impact: Delivers a comprehensive spatial framework for uterine gland morphogenesis, clarifying how compartment-specific signaling networks coordinate postnatal uterine maturation.
Jamaluddin MFB et al., https://doi.org/10.1073/pnas.2600524123
🧠 Neurodevelopment & Brain Isoform Biology
Whole-transcriptome-scale isoform-resolved spatial imaging of single cells in tissues.
(Also relevant as a neurobiology resource.) Applied to mouse brain, this isoform-resolved MERFISH workflow uncovers brain regions and cell types with particularly rich isoform diversity, illuminating how alternative splicing contributes to local circuit specialization. Spatial analyses of ligand–receptor interactions add a cell–cell communication layer to the atlas.
Impact: Creates a high-dimensional spatial isoform atlas of the mouse brain that will serve as a foundational reference for neurobiology and circuit-mapping studies.
Cohen L et al., https://doi.org/10.1016/j.cell.2026.06.027
🧴 Dermatology & Skin Immunology
Single-cell transcriptome reveals keratinocyte subclusters contributing to altered differentiation and inflammatory responses in atopic dermatitis.
Profiling lesional and non-lesional skin from atopic dermatitis patients and healthy controls, this single-cell and spatial transcriptomics study identifies keratinocyte subclusters that drive disrupted differentiation trajectories and heightened inflammatory responses. Disease-specific regulators (APOD, LYZ, SERPINB4) and a pathogenic KC subset (DK6) show mitochondrial/ER stress, while spatial analysis highlights TWEAK signaling from IL-13–responsive immune cells as a key lesional interaction.
Impact: Pinpoints spatially and transcriptionally distinct keratinocyte programs at the core of atopic dermatitis pathology, revealing candidate therapeutic targets and biomarkers.
Qin T et al., https://doi.org/10.1038/s41467-026-75407-9
🚬 Cancer Research & Genomic Instability
Multiomic profiling links L1 retrotransposition to genomic instability and ecDNA in bladder cancer.
In a 48-patient bladder cancer cohort, integrated analysis of cell-free DNA, long-read tumor DNA, RNA-seq, and spatial transcriptomics shows that somatic LINE-1 (L1) insertions are frequent, early events that drive downstream structural rearrangements and extrachromosomal DNA (ecDNA) formation. Spatial mapping reveals heterogeneous ecDNA enrichment across tissue architecture, associated with APOBEC3B expression and immune response pathways, supporting a model where L1 activity fuels genomic instability and viral mimicry.
Impact: Connects spatially mapped L1 retrotransposition to ecDNA burden and immune signaling in bladder cancer, suggesting new angles for prognosis and therapeutic targeting of genome instability.
Pribus SJ et al., https://doi.org/10.1038/s41467-026-75399-6