ArticleGenome biology2024
An integrated single-cell RNA-seq map of human neuroblastoma tumors and preclinical models uncovers divergent mesenchymal-like gene expression programs.
Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed.
- Single-cell and spatial omics reveals region-specific plasticity and therapeutic vulnerabilities in metastatic high-risk neuroblastoma.Science advances · 2026Article
- The Single-Cell Pediatric Cancer Atlas: Data portal and open-source tools for single-cell transcriptomics of pediatric tumors.Cell genomics · 2026Article
- Hypoxia-Induced Lineage Plasticity in Neuroblastoma: Advancing Signature Interpretation and Clinical Translation.Clinical and translational science · 2026Article
- Article
- Alternative Splicing of the NF-Y Subunit, NF-YA, in Neuroblastoma Phenotype Heterogeneity.Cancers · 2026Review
- Single-Cell and Spatial Omics: Methods and Applications.MedComm · 2026Review
- Hypoxia Promotes an Adrenergic to Mesenchymal Transcriptional Program Transition in Neuroblastoma.Clinical and translational science · 2026Article
- Intercellular Horizontal Transfer of TXNDC5 mRNA via Extracellular Vesicles Contributes to Tumor-Associated Macrophage-Mediated Prostate Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Identification of a novel PANoptosis-associated prognostic signature and immune landscape analysis in neuroblastoma with experimental validation.Frontiers in immunology · 2026Article
- Chromosomal instability degrades developmental phenotypes essential for anti-GD2 immunotherapy outcomes in high-risk neuroblastoma.Cell reports. Medicine · 2025Article
- Single-cell and Spatial Omics Reveals Region-Specific Plasticity and Therapeutic Vulnerabilities in Metastatic High-Risk Neuroblastoma.bioRxiv : the preprint server for biology · 2025Article
- Regulation and dysregulation of microRNA - transcription factor axes in differentiation and neuroblastoma.Cellular and molecular life sciences : CMLS · 2025Review
- Emerging artificial intelligence-driven precision therapies in tumor drug resistance: recent advances, opportunities, and challenges.Molecular cancer · 2025Review
- Latent epigenetic programs in Müller glia contribute to stress and disease response in the retina.Developmental cell · 2025Article
- Transcriptionally distinct malignant neuroblastoma populations show selective response to adavosertib treatment.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Bone morphogenetic protein (BMP) signaling determines neuroblastoma cell fate and sensitivity to retinoic acid.Nature communications · 2025Article
- CSI-GEP: A GPU-based unsupervised machine learning approach for recovering gene expression programs in atlas-scale single-cell RNA-seq data.Cell genomics · 2025Article
- Cell state plasticity in neuroblastoma.EJC paediatric oncology · 2024Article
- A spatial cell atlas of neuroblastoma reveals developmental, epigenetic and spatial axis of tumor heterogeneity.bioRxiv : the preprint server for biology · 2024Article
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23 authors.
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Abstract
backgroundNeuroblastoma is a common pediatric cancer, where preclinical studies suggest that a mesenchymal-like gene expression program contributes to chemotherapy resistance. However, clinical outcomes remain poor, implying we need a better understanding of the relationship between patient tumor heterogeneity and preclinical models.
resultsHere, we generate single-cell RNA-seq maps of neuroblastoma cell lines, patient-derived xenograft models (PDX), and a genetically engineered mouse model (GEMM). We develop an unsupervised machine learning approach ("automatic consensus nonnegative matrix factorization" (acNMF)) to compare the gene expression programs found in preclinical models to a large cohort of patient tumors. We confirm a weakly expressed, mesenchymal-like program in otherwise adrenergic cancer cells in some pre-treated high-risk patient tumors, but this appears distinct from the presumptive drug-resistance mesenchymal programs evident in cell lines. Surprisingly, however, this weak-mesenchymal-like program is maintained in PDX and could be chemotherapy-induced in our GEMM after only 24 h, suggesting an uncharacterized therapy-escape mechanism.
conclusionsCollectively, our findings improve the understanding of how neuroblastoma patient tumor heterogeneity is reflected in preclinical models, provides a comprehensive integrated resource, and a generalizable set of computational methodologies for the joint analysis of clinical and pre-clinical single-cell RNA-seq datasets.
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