ArticleThe Journal of clinical investigation2023
Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed, 178 citations in OpenAlex.
- Identification of cancer-associated fibroblast biomarkers in cutaneous squamous cell carcinoma.Oncology letters · 2026Article
- Decoding epithelial-mesenchymal transitions with multi-omics.Nature reviews. Genetics · 2026Review
- Unveiling the role of spatial transcriptomics in the analysis of the tumor immune microenvironment (Review).International journal of molecular medicine · 2026Review
- Biomimetic Scaffold-Based 3D Models for Decoding Cancer Biology and Advancing Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- FAPExperimental & molecular medicine · 2026Article
- Tumor-Derived LAMB3 Drives Immunosuppressive LRRC15Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatial transcriptomics in cancer research: insights into tumorigenesis, diagnosis and therapeutics.Cell death discovery · 2026Review
- Spatial multi-omics unveils the monoclonal origin, neuroendocrine plasticity, and microenvironment niches in combined small-cell lung cancer.Cell reports. Medicine · 2026Article
- Decoding the CAF-TAM axis: multi-omics dissection and therapeutic targeting of stromal-immune crosstalk in the tumor microenvironment.Cell death & disease · 2026Review
- Precision Immunotherapeutics for Glioblastoma: Current Approaches and Emerging Strategies in 2026.Cells · 2026Review
- Heat up and Destroy: Immunotherapy of "Cold" Tumors Using the Example of Glioblastoma.International journal of molecular sciences · 2026Review
- Redefining the immune microenvironment of gliomas in the era of single-cell genomics.Neuro-oncology advances · 2026Review
- A spatially resolved human glioblastoma atlas reveals distinct cellular and molecular patterns of anatomical niches.Nature communications · 2026Article
- GLUL Confers Perivascular Cancer-Associated Fibroblasts With Pro-Angiogenic Capacity to Promote Glioma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- From the brain cell atlas to precision neurology: a review of the application of AI-driven multi-omics in brain science.GigaScience · 2026Review
- CellMap: precision mapping of cellular landscape in spatial transcriptomics.Nucleic acids research · 2026Article
- Defining neurovascular ecosystem states with single-cell multi-omics and machine learning: insights into cerebrovascular remodeling in the tumor context.Frontiers in cell and developmental biology · 2026Article
- Pericyte-derived cancer-associated fibroblasts correlate with poor survival and are enriched after chemoradiotherapy in glioblastoma.PloS one · 2026Article
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
75 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 2 institutions in 2 countries.
Funding
Abstract
Cancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization of glioblastoma specimens yielded cells with CAF morphology and single-cell transcriptomic profiles based on their lack of copy number variations (CNVs) and elevated individual cell CAF probability scores derived from the expression of 9 CAF markers and absence of 5 markers from non-CAF stromal cells sharing features with CAFs. Cells without CNVs and with high CAF probability scores were identified in single-cell RNA-Seq of 12 patient glioblastomas. Pseudotime reconstruction revealed that immature CAFs evolved into subtypes, with mature CAFs expressing actin alpha 2, smooth muscle (ACTA2). Spatial transcriptomics from 16 patient glioblastomas confirmed CAF proximity to mesenchymal glioblastoma stem cells (GSCs), endothelial cells, and M2 macrophages. CAFs were chemotactically attracted to GSCs, and CAFs enriched GSCs. We created a resource of inferred crosstalk by mapping expression of receptors to their cognate ligands, identifying PDGF and TGF-β as mediators of GSC effects on CAFs and osteopontin and HGF as mediators of CAF-induced GSC enrichment. CAFs induced M2 macrophage polarization by producing the extra domain A (EDA) fibronectin variant that binds macrophage TLR4. Supplementing GSC-derived xenografts with CAFs enhanced in vivo tumor growth. These findings are among the first to identify glioblastoma CAFs and their GSC interactions, making them an intriguing target.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.