ArticleNeuro-oncology2022
Comparative single-cell RNA-sequencing profiling of BMP4-treated primary glioma cultures reveals therapeutic markers.
Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- A State-Resolved Single-Cell and Spatial Atlas RevealsMedComm · 2026Article
- Novel curcumin derivative DMC-GF suppresses glioblastoma growth by targeting MAPK1 and TRIM21 to modulates STAT3/AKT phosphorylation.Discover oncology · 2026Article
- Cytokine CCL2 secreted by cancer-associated fibroblasts augments temozolomide resistance in glioblastoma through ERK1/2 signaling.Oncogene · 2025Article
- Significance of the association between hypoxia and pyroptosis-related genes in the prognostic prediction of glioblastoma: insights from model construction and validation.Translational cancer research · 2025Article
- Virtual Clinical Trials of BMP4 Differentiation Therapy: Digital Twins to Aid Successful Glioblastoma Trial Design.bioRxiv : the preprint server for biology · 2025Article
- Review
- p21-Dependent Senescence Induction by BMP4 Renders Glioblastoma Cells Vulnerable to Senolytics.International journal of molecular sciences · 2025Article
- Recent Advances in the Delivery of Bone Morphogenetic Proteins for Targeting Glioma: An Updated Review.International journal of nanomedicine · 2025Review
- Breed-Associated Differences in Differential Gene Expression Following Immunotherapy-Based Treatment of Canine High-Grade Glioma.Animals : an open access journal from MDPI · 2024Article
- BMP4 and Temozolomide Synergize in the Majority of Patient-Derived Glioblastoma Cultures.International journal of molecular sciences · 2024Article
- The TGF-β Family in Glioblastoma.International journal of molecular sciences · 2024Review
- Genomic Exploration of Distinct Molecular Phenotypes Steering Temozolomide Resistance Development in Patient-Derived Glioblastoma Cells.International journal of molecular sciences · 2023Article
- Review
- An Early Neoplasia Index (ENI10), Based on Molecular Identity of CD10 Cells and Associated Stemness Biomarkers, is a Predictor of Patient Outcome in Many Cancers.Cancer research communications · 2023Article
- Local delivery of hrBMP4 as an anticancer therapy in patients with recurrent glioblastoma: a first-in-human phase 1 dose escalation trial.Molecular cancer · 2023Article
- Delineating the glioblastoma stemness by genes involved in cytoskeletal rearrangements and metabolic alterations.World journal of stem cells · 2023Review
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlioblastoma (GBM) is the most aggressive primary brain tumor. Its cellular composition is very heterogeneous, with cells exhibiting stem-cell characteristics (GSCs) that co-determine therapy resistance and tumor recurrence. Bone Morphogenetic Protein (BMP)-4 promotes astroglial and suppresses oligodendrocyte differentiation in GSCs, processes associated with superior patient prognosis. We characterized variability in cell viability of patient-derived GBM cultures in response to BMP4 and, based on single-cell transcriptome profiling, propose predictive positive and early-response markers for sensitivity to BMP4.
methodsCell viability was assessed in 17 BMP4-treated patient-derived GBM cultures. In two cultures, one highly-sensitive to BMP4 (high therapeutic efficacy) and one with low-sensitivity, response to treatment with BMP4 was characterized. We applied single-cell RNA-sequencing, analyzed the relative abundance of cell clusters, searched for and identified the aforementioned two marker types, and validated these results in all 17 cultures.
resultsHigh variation in cell viability was observed after treatment with BMP4. In three cultures with highest sensitivity for BMP4, a substantial new cell subpopulation formed. These cells displayed decreased cell proliferation and increased apoptosis. Neuronal differentiation was reduced most in cultures with little sensitivity for BMP4. OLIG1/2 levels were found predictive for high sensitivity to BMP4. Activation of ribosomal translation (RPL27A, RPS27) was up-regulated within one day in cultures that were very sensitive to BMP4.
conclusionThe changes in composition of patient-derived GBM cultures obtained after treatment with BMP4 correlate with treatment efficacy. OLIG1/2 expression can predict this efficacy, and upregulation of RPL27A and RPS27 are useful early-response markers.
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