🫀 Cardiovascular & Metabolic Disease
Targeting modulated vascular smooth muscle cells in atherosclerosis via FAP-directed immunotherapy
Using multiomic single-cell profiling, epitope mapping, and spatial transcriptomics across 27 human coronary arteries, this study identifies fibroblast activation protein (FAP) as a robust marker of modulated vascular smooth muscle cells (VSMCs) driving atherosclerotic coronary artery disease. Lineage tracing in mice supports FAP as a selective target on pathogenic VSMC states, opening the door for precision immunotherapy in atherosclerosis.
Impact: Positions FAP-directed immunotherapy as a promising strategy to selectively target disease-driving smooth muscle cell states in coronary artery disease.
Amrute JM et al., https://doi.org/10.1126/science.adx1736
🧫 Immunology & Infection
A temporal and spatial atlas of adaptive immune responses in the lymph node following viral infection
This work introduces AIR-SPACE, an approach that integrates high-resolution spatial transcriptomics with long-read TCR/BCR sequencing to map adaptive immune responses in lymph nodes. Applying AIR-SPACE to vaccinia virus–infected mouse lymph nodes across five time points, the authors reveal dynamic IFN-γ–rich activation niches, subanatomical germinal center structures, and clonal sharing of B cells across multiple germinal centers.
Impact: Provides a high-resolution spatial-temporal atlas and toolkit to dissect adaptive immune responses within lymphoid tissues.
Jiang S et al., https://doi.org/10.1073/pnas.2504742123
🎗️ Cancer Research
Spatial transcriptomics reveals tumor microenvironment-driven subtypes of invasive lobular carcinoma
By applying spatial transcriptomics to 43 HR+/HER2− invasive lobular carcinoma (ILC) samples, this study dissects tumor and microenvironmental architecture and uncovers marked inter- and intratumor heterogeneity. Integrating spatial gene expression, histology, and deconvolution, the authors define four TME-driven subtypes (ILC4TME) that stratify prognosis and outperform existing signatures in multivariable models.
Impact: Delivers a clinically relevant spatially informed classification of ILC that refines risk stratification and therapeutic targeting.
Serra M et al., https://doi.org/10.1073/pnas.2517567123
Neoadjuvant modified FOLFIRINOX plus nivolumab in borderline-resectable pancreatic ductal adenocarcinoma: a pilot phase 1 trial
In a neoadjuvant phase 1b/2 trial of borderline-resectable pancreatic ductal adenocarcinoma, modified FOLFIRINOX plus nivolumab met safety and pathologic response endpoints, enabling surgery in 79% of patients with encouraging survival outcomes. Spatial transcriptomics and immune profiling revealed increased intratumoral plasma cells, CD8 T cells, and lymphoid aggregates enriched for terminally exhausted CD8 T cells in treated tumors versus chemotherapy-only controls.
Impact: Demonstrates the feasibility and biological impact of adding immunotherapy to neoadjuvant chemotherapy in PDAC, supported by spatially resolved immune remodeling.
Wainberg ZA et al., https://doi.org/10.1038/s41467-026-68976-2
CD8+ T cells in the tumor microenvironment modulate the response to endocrine therapy in breast cancer
Analyzing pre- and on-treatment biopsies from HR+ breast cancer patients on letrozole, the authors show that endocrine therapy–resistant tumors harbor higher stromal TILs and immune gene signatures, particularly CXCL9/10/11–CXCR3 signaling. Spatial transcriptomics and functional assays reveal that CD8+ T cell–associated CXCL11 promotes ER+ tumor cell growth under estrogen deprivation via CXCR3/CXCR7, driving resistance.
Impact: Identifies a CXCL11–CXCR3/7 axis, spatially linked to CD8+ T cells, as a mediator of endocrine resistance and a potential therapeutic target in HR+ breast cancer.
Napolitano F et al., https://doi.org/10.1172/JCI188458
Lymph node colonization induces tissue remodeling via immunosuppressive fibroblast-myeloid cell niches supporting metastatic tolerance
Using spatial proteomics, spatial transcriptomics, and in vivo models, this study shows that metastatic colonization of lymph nodes in head-and-neck cancer induces interferon-γ–associated, immunosuppressive niches composed of myeloid cells and CAFs. These niches intersect with T cell zones and follicles, driving T cell dysfunction and Treg activation and extending immunosuppressive remodeling into adjacent, tumor-free lymph nodes.
Impact: Establishes lymph node metastases as active organizers of systemic immunosuppression via spatially defined myeloid–fibroblast niches, with implications for metastasis-directed therapy.
Haist M et al., https://doi.org/10.1016/j.ccell.2026.01.003
🧠 Neurobiology & Brain Development
A spatiotemporal atlas of cerebrovascular development in zebrafish
Combining in situ sequencing, single-cell transcriptomics, and 3D vascular reconstruction, this work maps zebrafish brain endothelial development from 3–11 dpf, capturing a transition from lateral vascularization to intraparenchymal angiogenesis as the blood–brain barrier (BBB) matures. The authors identify conserved endothelial subtypes, stage-specific capillary gene modules for transport and tight junctions, and show that perturbing three CapEC-enriched genes disrupts vascular patterning and BBB integrity.
Impact: Provides a multiscale spatial atlas of cerebrovascular development and BBB maturation with conserved insights relevant to mammalian brain vasculature.
Li X et al., https://doi.org/10.1038/s41467-026-68995-z
An in vivo and in vitro spatiotemporal profile of human midbrain development
This study integrates single-cell and spatial transcriptomics of first and second trimester human fetal midbrain with in vitro midbrain models to benchmark how faithfully organoids recapitulate human development. The authors reveal that brain organoids most closely resemble late first trimester tissue, reconstruct neuronal and astrocytic maturation trajectories, and use spatial context to align organoid architecture and signaling with second trimester midbrain, validating disease modeling in dopamine transporter deficiency.
Impact: Delivers a reference spatial atlas to calibrate and validate human midbrain organoid models for neurodevelopment and disease research.
Budinger D et al., https://doi.org/10.1038/s41467-025-67779-1
Molecular signatures of resilience to Alzheimer’s disease in neocortical layer 4 neurons
Using single-nucleus and spatial transcriptomics across neocortical regions with differential vulnerability to Alzheimer’s disease, the authors identify a resilient layer 4 excitatory neuron population expressing RORB, CUX2, and EYA4. These neurons show early upregulation of synaptic, calcium homeostasis, and neuroprotective genes and highlight KCNIP4 as a key resilience factor, whose overexpression in an AD mouse model confers protection against pathology.
Impact: Pinpoints spatially defined, molecularly resilient neuron populations and targets like KCNIP4 that could inform neuroprotective strategies in Alzheimer’s disease.
Dharshini SAP et al., https://doi.org/10.1038/s41467-026-68920-4
🧪 Technology & Methods Development
A spectral dimension reduction technique that improves pattern detection in multivariate spatial data
This Bioinformatics paper introduces a spectral dimension reduction method tailored for multivariate spatial transcriptomics, designed to enhance detection of spatial patterns across many genes. By leveraging spatial structure during dimensionality reduction, the technique improves sensitivity to complex spatial organization compared to conventional methods.
Impact: Provides a statistically grounded tool to better extract and visualize biologically meaningful spatial patterns from high-dimensional spatial omics datasets.
Köhler D et al., https://doi.org/10.1093/bioinformatics/btag052