🧠Neurobiology
An opposing molecular gradient axis underlies primate cortical organization.
By integrating spatial transcriptomics, MRI, and retrograde labeling in marmosets, this study uncovers two opposing molecular gradients that organize primate cortical areas and refine postnatally. These gradients align with thalamic gene expression and projection patterns, reconcile competing theories of cortical expansion, and reveal shared molecular features of the default mode network and frontal pole in humans and marmosets.
Impact: Defines a fundamental gradient-based organizing principle of the primate cortex with cross-species relevance.
Huang Z et al., https://doi.org/10.1126/science.aea2673
The spatiotemporal dynamics of postnatal vascularization in the mouse brain.
Using an optically cleared, light‑sheet aligned brain atlas (LAMBADA) combined with spatial transcriptomics, the authors map three brain‑wide phases of postnatal vascular development: isometric expansion, regional specialization, and refinement. They link structural remodeling of the vasculature to distinct molecular programs and neuronal maturation across time and space.
Impact: Provides a high-resolution spatiotemporal atlas for dissecting neurovascular development and maturation in the postnatal brain.
de Launoit E et al., https://doi.org/10.1016/j.cell.2026.03.013
Spatial and single-cell transcriptomic atlas of human suprachiasmatic nucleus.
Combining spatial transcriptomics, single-nucleus RNA-seq, and deep-learning-based histology, this work builds a comprehensive molecular and cellular atlas of the adult human suprachiasmatic nucleus (SCN). The study identifies seven neuron subtypes with spatially distinct distributions, reveals conserved circuit organization across species, and links specific AVP/NMS neurons to human chronotype genetics.
Impact: Delivers a reference atlas of the human circadian pacemaker that connects cellular SCN architecture to sleep–wake phenotypes.
Yang Q et al., https://doi.org/10.1016/j.neuron.2025.12.032
🧪 Technology & Methods Development
RESCUE: recovery of unattributed expression patterns in spatial transcriptomics.
This paper introduces RESCUE, a computational method that recovers gene expression signals systematically missed by standard cell segmentation and deconvolution workflows in spatial transcriptomics. By capturing transcripts from fragile or rare cell types, subcellular structures, and extracellular RNA, RESCUE reveals additional spatial expression patterns and improves biological interpretation across multiple datasets, including MERFISH in honey bee brain.
Impact: A powerful analysis tool to reclaim “lost” spatial expression, reducing bias and uncovering hidden biology in spatial omics datasets.
Lee YJ et al., https://doi.org/10.1038/s41467-026-71720-5
🧬 Cancer Research
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 with spontaneous p53 loss, the authors pinpoint a progenitor-like cell population where oncogenic KRAS and tumor-suppressive programs (p53, CDKN2A, SMAD4) are co-activated. They show that this spatially defined niche undergoes stepwise remodeling toward invasive PDAC, is sensitive to transient KRAS inhibition, and is expanded by p53 suppression, which promotes EMT and immune-privileged microenvironments.
Impact: Identifies a spatially confined progenitor niche as a key intervention window for intercepting the benign-to-malignant transition in pancreatic cancer.
Reyes J et al., https://doi.org/10.1016/j.cell.2026.03.032
Spatial multiomics profiling reveals ZFP36-mediated immunometabolic reprogramming in bladder cancer.
By integrating spatial metabolomics and spatial transcriptomics, this study maps heterogeneous metabolic and immune landscapes across bladder cancer regions and highlights ZFP36 as a central regulator of immunometabolic reprogramming. Functional experiments show that Zfp36 loss lowers T cell activation thresholds, boosts intratumoral T cell infiltration, and synergizes with anti–PD‑1 therapy, while mechanistic work links ZFP36 to degradation of immune-regulatory mRNAs such as C1QBP.
Impact: Positions ZFP36 as a promising immunometabolic target and demonstrates the power of spatial multiomics for guiding bladder cancer immunotherapy.
Ye F et al., https://doi.org/10.1073/pnas.2505125123
Clonal biases dictate availability of colonic cancer driver mutations for transformation.
Targeted sequencing of 76,800 normal colonic glands from 56 individuals reveals that canonical colorectal cancer driver mutations in APC, KRAS, TP53, FBXW7, and CTNNB1 are already present in histologically normal tissue. Clonal reconstruction and spatial transcriptomics show distinct fixation and expansion behaviors—for example, FBXW7 R465C mutants tend to fix in tissue, while KRAS G12 mutants expand—and link a mixed-lineage KRAS mutant state to elevated transformation risk.
Impact: Illuminates how clonal behavior and spatial phenotypes of driver-mutant clones in normal colon shape cancer initiation risk.
Skoufou-Papoutsaki N et al., https://doi.org/10.1038/s41467-026-71944-5
🧬 Immunology & Autoimmunity
Polyclonal selection of immune checkpoint mutations in thyroid autoimmunity.
Focusing on how self-reactive lymphocytes escape immune tolerance, this study tests the hypothesis that somatic mutations in immune-regulatory genes accumulate in autoimmune thyroid disease. The authors uncover polyclonal selection of immune checkpoint mutations in self-reactive lymphocytes, suggesting that multiple, independently acquired genetic hits allow these cells to bypass checkpoints and drive autoimmunity.
Impact: Reveals somatic immune checkpoint mutations as a polyclonal mechanism enabling chronic thyroid autoimmunity.
Nicola PA et al., https://doi.org/10.1038/s41586-026-10493-9
JAK inhibitors alleviate EGFR-inhibitor-induced diarrhea by protecting intestinal stem cells from adaptive-immune-exacerbated injury.
Using spatial transcriptomics and mechanistic models, this work shows that EGFR tyrosine kinase inhibitors suppress jejunal intestinal stem cell proliferation via chemokine-driven T and B cell recruitment and IFN‑γ/TNF-mediated damage. Targeted JAK inhibition interrupts IFN‑γ–JAK/STAT signaling in stem cells, restores mucosal repair, and mitigates EGFRi-induced diarrhea without substantially compromising antitumor effects.
Impact: Reframes EGFR inhibitor enteropathy as an immune-driven, spatially organized stem cell injury and proposes JAK inhibition as a rational supportive therapy.
Cheng Y et al., https://doi.org/10.1038/s41467-026-71739-8
🧫 Tissue & Organ Atlases
A spatial atlas of the healthy human liver from live donors.
Addressing the scarcity of truly healthy human tissue, this study constructs a spatial gene expression atlas of the human liver using samples from live donors rather than post-mortem or peri-diseased tissue. The atlas captures physiologic zonation and cell-type-specific expression without ischemic or disease-associated artifacts, enabling more accurate references for liver biology and pathology.
Impact: Provides a gold-standard spatial transcriptomic reference of healthy human liver directly from live donors.
Yakubovsky O et al., https://doi.org/10.1038/s41586-026-10377-y