🧫 Immunology & Reproductive Biology
Eosinophils drive intestinal remodelling and innate defence in reproduction.
This study reveals that eosinophils are key orchestrators of intestinal remodeling and innate defense during mammalian reproduction, counterbalancing the immune tolerance that develops in pregnancy. By mapping immune adaptations in the gut, the work links local barrier immunity to reproductive success and species fitness.
Impact: Positions eosinophils as central regulators of gut immunity and tissue remodeling in pregnancy, with implications for maternal health and fertility.
Huang C et al., https://doi.org/10.1038/s41586-026-10531-6
🎯 Cancer Research & Tumor Evolution
Oncogenic and tumor-suppressive forces converge on a progenitor niche at the benign-to-malignant transition.
Using single-cell and spatial transcriptomics in mouse models of pancreatic ductal adenocarcinoma, this work identifies a discrete progenitor-like niche where oncogenic KRAS and tumor-suppressive pathways (p53, CDKN2A, SMAD4) are co-activated and engage senescence-like programs. Spatial remodeling of this niche tracks with malignant progression, and manipulating KRAS or p53 shifts its size, epithelial–mesenchymal state, and immune privilege to delay or accelerate tumor initiation.
Impact: Defines a spatially localized progenitor niche as the key convergence point for malignant transition in PDAC, revealing a therapeutic window for cancer interception.
Reyes J et al., https://doi.org/10.1016/j.cell.2026.03.032
In vivo CRISPR screens identify CBX4 as an epigenetic regulator for cancer immunotherapy.
In vivo CRISPR screens combined with single-cell and spatial transcriptomics identify CBX4 as an epigenetic brake on anti-tumor immunity in both tumor cells and immunosuppressive macrophages. Loss of CBX4 de-represses endogenous retroelements, activates RNA-sensing and type I IFN pathways, inflames the tumor microenvironment, and boosts responses to immune checkpoint blockade, particularly in hepatocellular carcinoma.
Impact: Establishes CBX4 as a druggable epigenetic immune checkpoint and biomarker to overcome resistance to cancer immunotherapy.
Ma Z et al., https://doi.org/10.1172/JCI200564
In Silico Reconstruction of Primary and Metastatic Tumor Architecture Using Geographic Information System-Augmented Spatial Transcriptomics.
The authors introduce GIS-ROTA, a GIS-augmented analysis framework that overlays pathway- and cell type–level enrichment onto spatial transcriptomics to define functionally meaningful tumor domains. Applied to ER+ primary and metastatic breast cancers, GIS-ROTA uncovers spatial co-localization of estrogen and metabolic programs and mutual exclusivity with metastasis- and immune-related pathways, providing interpretable maps of tumor architecture.
Impact: Delivers a biologically informed spatial analytics toolkit to reconstruct tumor ecosystems and identify spatially organized therapeutic targets.
Yoo JY et al., https://doi.org/10.1158/0008-5472.CAN-25-3161
Molecular insights into early malignant transition of hepatocellular carcinoma.
By profiling evolutionarily linked dysplastic nodules and very early hepatocellular carcinomas, this study shows that TERT alterations predispose lesions to malignancy, while the accumulation of copy number alterations is the main driver of malignant transition. Spatially and immunologically, cancer-prone nodules are immune-inactive, whereas many very early HCCs rapidly acquire an inflamed yet immune-evasive phenotype, delineating two distinct evolutionary routes.
Impact: Refines models of early hepatocarcinogenesis and highlights windows for immunotherapy-based interception at the premalignant and very early HCC stages.
Zhang Z et al., https://doi.org/10.1016/j.ccell.2026.03.005
🧠Neurobiology & Brain Circuits
Fronto-insular circuit mechanisms of accelerated intermittent theta burst stimulation.
Using an optogenetic mouse model of accelerated intermittent theta burst stimulation (aiTBS), this work shows that stimulation enhances plasticity-related gene expression, spine density, and excitatory currents in prefrontal intratelencephalic neurons. Whole-brain activity mapping and circuit manipulations pinpoint a fronto-insular network as necessary and sufficient for antidepressant-like effects, which is then validated in humans using intracortical EEG and resting-state fMRI.
Impact: Identifies a conserved fronto-insular circuit as the core mediator of aiTBS antidepressant effects, guiding more targeted neuromodulation strategies.
Johnson SB et al., https://doi.org/10.1016/j.cell.2026.04.030
The spatiotemporal dynamics of postnatal vascularization in the mouse brain.
This study presents LAMBADA, a light-sheet aligned, spatial transcriptomics–enriched developmental atlas of the mouse brain that tracks postnatal vascular growth and remodeling. The authors delineate three distinct, brain-wide phases of vascular development—expansion, regional specialization, and refinement—and link molecular programs to structural changes and neuronal maturation.
Impact: Provides a high-resolution spatiotemporal resource to decode neurovascular development and its perturbation in brain disease models.
de Launoit E et al., https://doi.org/10.1016/j.cell.2026.03.013
Single-cell multiomic and spatial landscape of the primate pineal gland reveals circadian and melatonin regulatory architecture.
Integrating snRNA-seq, snATAC-seq, and spatial transcriptomics in the macaque pineal gland, this study maps pinealocytes and diverse glial/vascular lineages and uncovers a dual-layer regulatory architecture: robust, spatially organized melatonin synthesis programs overlaid with more sparsely distributed circadian clock regulators. Network and cell–cell communication analyses identify key transcriptional hubs and signaling axes, and link sleep and neuropsychiatric risk variants to pineal regulatory modules.
Impact: Delivers a single-cell and spatial blueprint of primate pineal regulation that connects circadian biology to human sleep and psychiatric disease genetics.
Zheng J et al., https://doi.org/10.1073/pnas.2524839123
Optics-free spatial genomics for mapping mammalian brain aging by IRISeq.
The authors introduce IRISeq, an optics-free spatial genomics platform that reconstructs tissue architecture via indexed sequencing at tunable resolutions, enabling cost-effective, large-scale mapping. Applied to >70 mouse brain sections across aging and lymphocyte-deficient models, IRISeq reveals lymphocyte-dependent regional aging signatures, including altered interferon signaling, ependymal cell preservation, and distinct microglial state dynamics.
Impact: Establishes a scalable spatial transcriptomics technology and resource to dissect immune-dependent mechanisms of brain aging.
Abdulraouf A et al., https://doi.org/10.1038/s41593-026-02293-1
🛡️ Immunology & Tissue-Resident Immunity
Distinct tissue niches contribute to prostate tissue-resident memory CD8(+) T cell differentiation and heterogeneity.
This work dissects how different anatomical niches within the prostate shape the differentiation and functional diversity of tissue-resident memory CD8+ T cells in a key male barrier and cancer-prone organ. By integrating spatial and phenotypic profiling, the study links microenvironmental cues to TRM heterogeneity, with implications for infection control and tumor surveillance in the prostate.
Impact: Illuminates niche-specific programming of prostate-resident CD8+ T cells, informing strategies to harness TRM cells for infection and cancer immunotherapy.
Takehara KK et al., https://doi.org/10.1016/j.immuni.2026.03.003