Cholinergic neuron-to-glioblastoma synapses in a human iPSC-derived co-culture model.

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 profil

SUBMITTER: Sun Y 

PROVIDER: S-EPMC12277791 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature