This weeks top spatial transcriptomics paper
🧫 Cancer Research
Oncogenic function and transcriptional dynamics of MYCN in liver tumorigenesis.
Using a transposon-based mouse model, the authors show that MYCN overexpression synergizes with AKT activation to drive liver tumorigenesis and imprint stress-adaptive transcriptional programs characteristic of high-risk human HCC. Time-resolved spatial transcriptomics reveals a MYCN-enriched niche marked by EMT and Wnt/β-catenin signaling that expands during progression, enabling development of a machine learning–derived “MYCN niche score” that predicts recurrence from non-tumor liver tissue.
Impact: Establishes MYCN as a spatial biomarker of tumor-promoting niches in liver and delivers a clinically actionable score to stratify high-risk HCC patients from nontumor biopsies.
Qin XY et al., https://doi.org/10.1073/pnas.2521923123
Single-Cell Analysis of Chemotherapy-induced Remodeling Reveals CD276-driven Basal-like Chemoresistance in Pancreatic Cancer.
This study uses single-cell and spatially informed analysis of PDAC tumors before and after chemotherapy to map how treatment reshapes tumor cell states and the tumor microenvironment. The authors identify a CD276-driven basal-like cell population associated with chemoresistance, revealing molecular circuits and cellular interactions that sustain refractory disease.
Impact: Pinpoints a spatially and transcriptionally defined CD276+ basal-like compartment as a promising target to overcome chemoresistance in pancreatic cancer.
Zhang Y et al., https://doi.org/10.1053/j.gastro.2025.09.043
Spatial evidence for carcinoma in situ (CIS) as an entity in human papillomavirus (HPV)-associated tonsillar squamous cell carcinoma (TSCC).
Combining a systematic review with Visium spatial transcriptomics across HPV-associated TSCC, cervical cancer, and HPV-independent oral cancers, the authors show that tonsillar CIS and cervical HSIL share highly correlated expression profiles. Unsupervised epithelial clustering and trajectory analysis reveal dysplastic states and a continuous transition from dysplasia to invasion in TSCC, analogous to cervical carcinogenesis.
Impact: Provides spatial-transcriptomic evidence that CIS is a bona fide stage in HPV-associated TSCC, supporting the existence of pre-invasive tonsillar lesions and earlier detection windows.
Näsman T et al., https://doi.org/10.1002/ijc.70207
Histone acetyltransferase HAT1 drives malignant progression in lower-grade glioma: reshaping the immune microenvironment and molecular mechanisms.
The authors dissect the role of HAT1 in lower-grade glioma, integrating transcriptomic and spatially informed analyses to link high HAT1 expression with more aggressive molecular features. HAT1 upregulation is associated with immunosuppressive remodeling of the tumor microenvironment, including altered immune cell infiltration and checkpoint pathways that may fuel malignant progression.
Impact: Positions HAT1 as both a driver of glioma progression and a regulator of the immune microenvironment, nominating it as a dual-purpose biomarker and therapeutic target.
Sha Z et al., https://doi.org/10.1016/j.neuroscience.2026.02.011
Integration of TWAS with single-cell and spatial transcriptomics identifies TLR1 as a susceptibility gene and therapeutic target in the breast cancer tumor microenvironment.
By integrating GWAS with eQTL (TWAS), the study identifies five breast cancer susceptibility genes and then localizes their function using single-cell and spatial transcriptomics within the tumor microenvironment. These genes, particularly TLR1, are enriched in signaling pathways linked to myofibroblasts, mast cells, and M2 macrophages, and interact through MIF- and SPP1-mediated circuits; in silico drug screens highlight agents such as Doxorubicin and Etoposide as candidate TLR1-targeting therapies.
Impact: Bridges population genetics with spatial single-cell biology to pinpoint TLR1 and related genes as microenvironment-focused targets for precision breast cancer therapy.
Zhang J et al., https://doi.org/10.1016/j.ijbiomac.2026.150951
🧠 Neurobiology
Spatiotemporal histogenesis of the developing human cerebellum reveals dynamic layering of Bergmann glia.
Combining spatial transcriptomics, single-nucleus RNA-seq, and histology, this work builds a developmental atlas of human Bergmann glia (BG) from ~11 postconception weeks to term. The authors uncover an unexpected trilaminar organization—including a lamina dissecans separating BG from Purkinje cells—that emerges early and later merges, and appears unique to humans compared with mice, ferrets, and marmosets.
Impact: Delivers a human-specific spatial atlas of cerebellar Bergmann glia that revises developmental timelines and informs modeling of neurodevelopmental disorders.
He G et al., https://doi.org/10.1073/pnas.2525673123
🦷 Developmental Biology
Spatiotemporal interplay between epithelial and mesenchymal cells drives human dentinogenesis.
Using single-cell RNA sequencing and spatial transcriptomics across human tooth development from initiation to eruption, the authors map how dental epithelium (DE) instructs dental papilla (DP) cells to differentiate into odontoblasts. They propose a WNT–NOTCH sequential activation model and identify key signaling molecules, including DLX6-AS1, that coordinate epithelial–mesenchymal crosstalk during dentin formation.
Impact: Provides a high-resolution spatial atlas and mechanistic framework for human dentinogenesis, guiding strategies for tooth repair and regenerative dentistry.
Wei W et al., https://doi.org/10.1038/s41467-026-69545-3
🛡️ Immunology & Hematology
Local antibody feedback enforces a checkpoint on affinity maturation in the germinal center and promotes epitope spreading.
In mouse models with defined BCR affinities, the authors show that high-affinity B cells experience shortened germinal center residency and suppress lower-affinity clones targeting the same epitope, while local antibody feedback limits further affinity maturation. Spatial transcriptomics identifies plasma-like cells and early IgG production within and around germinal centers, supporting a self-regulating feedback loop that promotes epitope spreading toward alternative epitopes on a multivalent HIV Env immunogen.
Impact: Reveals a spatially organized antibody feedback mechanism that constrains affinity maturation and favors epitope spreading, informing rational vaccine and booster design.
Yan Y et al., https://doi.org/10.1016/j.immuni.2026.01.011
Single-cell multiomic atlas of healthy pediatric bone marrow reveals age-dependent differences in lineage differentiation driven by stromal signaling.
This study generates a multimodal single-cell atlas (mRNA + surface protein) of 90,710 cells from healthy pediatric bone marrow and complements it with spatial transcriptomics across ages 0–23 years. The authors show a shift from B cell–biased output in young children to myeloid and T cell bias in adolescents/young adults, driven by age-tuned stromal signaling and distinct lymphoid progenitor subsets that regulate lineage decisions.
Impact: Establishes a spatially anchored, age-resolved reference atlas of pediatric bone marrow to understand immune development and susceptibility to hematologic disease.
Hanemaaijer ES et al., https://doi.org/10.1038/s41590-026-02422-9
❤️ Cardiovascular Research
Spatial transcriptomics reveals a key role of fibroblast-like vascular smooth muscle cells in human atherosclerotic cell crosstalk and stability.
By applying spatial transcriptomics to human atherosclerotic plaques, the authors chart the localization and communication networks of diverse plaque cell phenotypes. They identify fibroblast-like vascular smooth muscle cells as central hubs in plaque microenvironments, mediating cell–cell crosstalk linked to inflammatory signaling and structural stability versus vulnerability.
Impact: Highlights fibroblast-like smooth muscle cells as spatially defined regulators of plaque behavior and potential targets to prevent atherosclerotic events.
Goncalves I et al., https://doi.org/10.1093/eurheartj/ehaf1091*