ArticleNeuro-oncology2026
Combined patch-clamp electrophysiology and single-cell genomic analysis reveal spiking tumor cells at the neocortical glioblastoma interface in humans.
Article in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Functional implications of atypical action potential generation in the (patho)physiological brain: from developmental program to glioma.Frontiers in neural circuits · 2026Review
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24 authors.
Funding
Abstract
backgroundElectrophysiological features of glioblastoma cells (GBCs) remain largely elusive, challenging our comprehension of glioblastoma pathophysiology. Spiking GABAergic-oligodendrocyte-progenitor (OPC) tumor cells were recently described in IDH-mutant glioma, correlating with prolonged patient survival. Here, we characterize single-cell features at the neocortical leading edge (LE) of glioblastoma patients using combined electrophysiological, morphological, and transcriptomic profiling.
methodsWe examined GBCs and non-tumor cells using acute and cultured organotypic slices of cancer-infiltrated neocortical tissues from glioblastoma patients. Electrophysiological properties of LE cells were investigated using whole-cell patch-clamp recording, with dye loading to characterize single-cell morphology. We used Patch-seq to determine the transcriptomic features of recorded LE cells and discriminate tumor and non-tumor cells, followed by gene set enrichment analysis and CellChat to identify differential gene expression and signaling.
resultsUpon depolarization, more than half of LE cells show aberrant action potentials (aAPs), akin to neurodevelopmental cells. Reconstructed LE cells have abnormal somatodendritic morphology. Patch-seq revealed that GBCs and non-tumor cells share a similar electrophysiological phenotype, including aAP generation, depolarized membrane potential, and elevated input resistance. Transcriptomic analysis shows that the aAP phenotype occurs across diverse GBC states and correlates with lower enrichment of proliferation-related pathways at the single-cell level, but higher enrichment of inflammatory/immune, angiogenic, and mesenchymal transition pathways. Non-tumor cells exhibit hybrid transcriptomic signatures, with predominantly neuronal but minor enrichment of astrocytic features.
conclusionWe find electrophysiological aAP behavior of GBCs in human glioblastoma, closely resembling that of hybrid cells in IDH-mutant glioma, supporting the hypothesis of neuronal mimicry across different glioma types.
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