ArticleStem cell reports2025
Cholinergic neuron-to-glioblastoma synapses in a human iPSC-derived co-culture model.
Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Modeling gliomas with organoids: Classification, fidelity, and guidelines for translational neuro-oncology.Neuro-oncology · 2026Review
- Harnessing human tumor organoids for cancer modeling and precision therapy.Protein & cell · 2026Review
- Neuro-glioma activity-dependent growth mechanisms: an actionable circuit from NLGN3-ADAM10 to AMPA synapses.Translational cancer research · 2026Review
- Pathological neural and immune synapses in glioblastoma progression: mechanisms and therapeutic opportunities.Frontiers in neural circuits · 2026Review
- Modeling gliomas with organoids: reconstructing the human neural microenvironment for translational neuro-oncology.Frontiers in oncology · 2026Review
- Glioma-neuron interactions: insights from neural plasticity.Frontiers in oncology · 2025Review
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Authors and funding
17 authors.
Funding
Abstract
Glioblastoma (GBM) integrates extensively into brain-wide neuronal circuits; however, neuron-tumor interactions have largely been studied with glutamatergic neurons in animal models. The role of neuromodulatory circuits for GBM biology in all-human cell systems remains unclear. Here, we report a co-culture system employing patient-derived GBM organoids and human induced pluripotent stem cell (hiPSC)-derived cholinergic neurons. We provided evidence of structural human cholinergic synaptic inputs onto GBM cells via trans-monosynaptic tracing and electron microscopy and functional synaptic interactions through the metabotropic CHRM3 receptor via calcium imaging. Deep single-cell RNA sequencing of co-cultures compared to GBM monocultures further revealed shifts in tumor transcriptional profiles toward a more proliferative state, with contributions from both diffusible factors and direct contacts, the latter of which are dependent on cholesterol biosynthesis. Together, our findings support the role of cholinergic inputs in promoting GBM progression and highlight hiPSC-derived co-culture models as a useful platform for cancer neuroscience.
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Registered trials
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