Single-cell transcriptome profiling reveals intra-tumoral heterogeneity in human chordomas
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Updated: Oct 5, 2025
Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting
Published on: September 25, 2012
Wanru Duan1,2, Boyan Zhang1, Xinqiang Li3
1Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Abstract:
Chordoma is a rare and aggressive bone tumor. An accurate investigation of tumor heterogeneity is necessary for the development of effective therapeutic strategies. This study aims to assess the poorly understood tumor heterogeneity of chordomas and identify potential therapeutic targets. Single-cell RNA sequencing was performed to delineate the transcriptomic landscape of chordomas. Six tumor samples of chordomas were obtained, and 33,737 cells passed the quality control test and were analyzed. The main cellular populations identified with specific markers were as follows: chordoma cells (16,052 [47.6%]), fibroblasts (6945 [20.6%]), mononuclear phagocytes (4734 [14.0%]), and T/natural killer (NK) cells (3944 [11.7%]). Downstream analysis of each cell type was performed. Six subclusters of chordomas exhibited properties of an epithelial-like extracellular matrix, stem cells, and immunosuppressive activity. Although few immune checkpoints were detected on cytotoxic immune cells such as T and NK cells, a strong immunosuppressive effect was exerted on the Tregs and M2 macrophages. In addition, the cellular interactions were indicative of enhancement of the TGF-β signaling pathway being the main mechanism for tumor progression, invasion, and immunosuppression. These findings, especially from the analysis of molecular targeted therapy and tumor immune microenvironment, may help in the identification of therapeutic targets in chordomas.
Insights
This study reveals chordoma tumor heterogeneity using single-cell RNA sequencing. Findings highlight immunosuppressive mechanisms and the TGF-β pathway, offering potential therapeutic targets for this aggressive bone cancer.
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Chordoma is a rare, aggressive bone tumor requiring better therapeutic strategies.
- Understanding tumor heterogeneity is crucial for developing effective treatments.
Purpose of the Study:
- To investigate chordoma tumor heterogeneity at a single-cell level.
- To identify potential therapeutic targets and understand the tumor immune microenvironment.
Main Methods:
- Single-cell RNA sequencing was performed on six chordoma samples.
- Analysis included 33,737 cells, identifying major cell populations: chordoma cells, fibroblasts, mononuclear phagocytes, and T/NK cells.
Main Results:
- Six chordoma subclusters showed epithelial-like ECM, stem cell, and immunosuppressive properties.
- A strong immunosuppressive effect was observed on Tregs and M2 macrophages, despite low immune checkpoints on cytotoxic cells.
- Cellular interactions indicated TGF-β signaling pathway enhancement drives tumor progression, invasion, and immunosuppression.
Conclusions:
- The study elucidates chordoma's complex cellular and molecular landscape.
- Targeting the TGF-β pathway and modulating the tumor immune microenvironment are promising therapeutic avenues for chordoma.
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