ArticleCell discovery2022
Single-cell transcriptome reveals cellular hierarchies and guides p-EMT-targeted trial in skull base chordoma.
Article in Cell discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Single-cell and spatial transcriptomics analysis of osteoarthritis: pathway regulation, cell interaction networks, and therapeutic translation.Journal of translational medicine · 2026Review
- Exacerbation of neuronal senescence after spinal cord injury: Role of the macrophage-derived transforming growth factor-β1-SMAD2 signaling axis.Neural regeneration research · 2026Article
- Platelets as localized conduits of TGF-β1 in the tumor microenvironment: implications for cancer progression and therapy.Human cell · 2026Review
- From Histology to Multi-Omics: Review of Chordoma Classification and Its Clinical Implications.Cells · 2026Review
- Immune and stromal signaling networks in chordoma: an evidence-weighted review of ligand-receptor interactions and therapeutic implications.Systematic reviews · 2026Review
- Wnt11 mediates fibroblast-smooth muscle cell interaction to promote neurogenic bladder fibrosis in rats.Communications biology · 2026Article
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Macrophage efferocytosis mediated by the TP63-RAC2 pathway promotes immunosuppressive remodeling in esophageal cancer.Cell reports. Medicine · 2026Article
- Neuronal inflammatory genes-based machine learning model for breast cancer: a novel perspective on clinical prognosis and tumor immunity.Discover oncology · 2025Article
- CXCR4 confers stemness and radioresistance in chordoma cells.Cancer biology & therapy · 2025Article
- USP20 competitively binds to STUB1 to enhance CTSL expression and promote epithelial-mesenchymal transition in head and neck squamous cell carcinoma.Clinical and translational medicine · 2025Article
- Cancer-associated fibroblast heterogeneity in chordomaThe Journal of pathology · 2025Article
- A Boolean network model of hypoxia, mechanosensing and TGF-β signaling captures the role of phenotypic plasticity and mutations in tumor metastasis.PLoS computational biology · 2025Article
- Combinatorial therapies for epigenetic, immunotherapeutic, and genetic targeting of chordoma.Journal of neuro-oncology · 2025Review
- Radiogenomic method combining DNA methylation profiles and magnetic resonance imaging radiomics predicts patient prognosis in skull base chordoma.Clinical epigenetics · 2025Article
- Integrated multiomics analysis identifies PHLDA1+ fibroblasts as prognostic biomarkers and mediators of biological functions in pancreatic cancer.Frontiers in immunology · 2025Article
- Single-cell and spatial omics unravel the spatiotemporal biology of tumour border invasion and haematogenous metastasis.Clinical and translational medicine · 2024Review
- Proteogenomic characterization of skull-base chordoma.Nature communications · 2024Article
- Epithelial-mesenchymal plasticity in cancer: signaling pathways and therapeutic targets.MedComm · 2024Review
- Single-cell RNA-seq reveals the transcriptional program underlying tumor progression and metastasis in neuroblastoma.Frontiers of medicine · 2024Article
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Skull base chordoma (SBC) is a bone cancer with a high recurrence rate, high radioresistance rate, and poorly understood mechanism. Here, we profiled the transcriptomes of 90,691 single cells, revealed the SBC cellular hierarchies, and explored novel treatment targets. We identified a cluster of stem-like SBC cells that tended to be distributed in the inferior part of the tumor. Combining radiated UM-Chor1 RNA-seq data and in vitro validation, we further found that this stem-like cell cluster is marked by cathepsin L (CTSL), a gene involved in the packaging of telomere ends, and may be responsible for radioresistance. Moreover, signatures related to partial epithelial-mesenchymal transition (p-EMT) were found to be significant in malignant cells and were related to the invasion and poor prognosis of SBC. Furthermore, YL-13027, a p-EMT inhibitor that acts through the TGF-β signaling pathway, demonstrated remarkable potency in inhibiting the invasiveness of SBC in preclinical models and was subsequently applied in a phase I clinical trial that enrolled three SBC patients. Encouragingly, YL-13027 attenuated the growth of SBC and achieved stable disease with no serious adverse events, underscoring the clinical potential for the precision treatment of SBC with this therapy. In summary, we conducted the first single-cell RNA sequencing of SBC and identified several targets that could be translated to the treatment of SBC.
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Registered trials
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.