Integrated electrophysiological and genomic profiles of single cells reveal spiking tumor cells in human glioma

Abstract Prior studies have described the complex interplay that exists between glioma cells and neurons, however, the electrophysiological properties endogenous to tumor cells remain obscure. To address this, we employed Patch-sequencing on human glioma specimens and found that one third of patched cells in IDH mutant (IDH mut ) tumors demonstrate properties of both neurons and glia by firing single, short action potentials. To define these hybrid cells (HCs) and discern if they are tumor in origin, we developed a computational tool, Single Cell Rule Association Mining (SCRAM), to annotate each cell individually. SCRAM revealed that HCs represent tumor and non-tumor cells that feature GABAergic neuron and oligodendrocyte precursor cell signatures. These studies are the first to characterize the combined electrophysiological and molecular properties of human glioma cells and describe a new cell type in human glioma with unique electrophysiological and transcriptomic properties that are likely also present in the non-tumor mammalian brain.