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

in Cancer cell by Rachel N Curry, Qianqian Ma, Malcolm F McDonald, Yeunjung Ko, Snigdha Srivastava, Pey-Shyuan Chin, Peihao He, Brittney Lozzi, Prazwal Athukuri, Junzhan Jing, Su Wang, Arif O Harmanci, Benjamin Arenkiel, Xiaolong Jiang, Benjamin Deneen, Ganesh Rao, Akdes Serin Harmanci

TLDR

  • The study found that some cells in the brain tumor called glioma have properties of both neurons and glia. These cells fire short action potentials and have features of GABAergic neurons and oligodendrocyte precursor cells. The study suggests that these cells may play a role in the development and progression of glioma and highlights the importance of using single-cell analysis techniques to better understand the complex cellular composition of glioma and other brain tumors.

Abstract

Prior studies have described the complex interplay that exists between glioma cells and neurons; however, the electrophysiological properties endogenous to glioma cells remain obscure. To address this, we employed Patch-sequencing (Patch-seq) on human glioma specimens and found that one-third of patched cells in IDH mutant (IDH) tumors demonstrate properties of both neurons and glia. To define these hybrid cells (HCs), which fire single, short action potentials, and discern if they are of tumoral origin, we developed the single cell rule association mining (SCRAM) computational tool to annotate each cell individually. SCRAM revealed that HCs possess select features of GABAergic neurons and oligodendrocyte precursor cells, and include both tumor and non-tumor cells. These studies characterize the combined electrophysiological and molecular properties of human glioma cells and describe a cell type in human glioma with unique electrophysiological and transcriptomic properties that may also exist in the non-tumor brain.

Overview

  • The study focuses on the complex interplay between glioma cells and neurons, specifically the electrophysiological properties of glioma cells. Patch-sequencing was employed on human glioma specimens to identify hybrid cells (HCs) that fire single, short action potentials and possess select features of GABAergic neurons and oligodendrocyte precursor cells. The study aims to characterize the combined electrophysiological and molecular properties of human glioma cells and describe a cell type in human glioma with unique electrophysiological and transcriptomic properties that may also exist in the non-tumor brain.

Comparative Analysis & Findings

  • The study found that one-third of patched cells in IDH mutant (IDH) tumors demonstrate properties of both neurons and glia. The single cell rule association mining (SCRAM) computational tool was developed to annotate each cell individually, revealing that HCs possess select features of GABAergic neurons and oligodendrocyte precursor cells, and include both tumor and non-tumor cells.

Implications and Future Directions

  • The study's findings suggest that hybrid cells may play a crucial role in the development and progression of glioma. Further research is needed to understand the mechanisms underlying the formation and function of these cells, as well as their potential as therapeutic targets. The study also highlights the importance of using single-cell analysis techniques to better understand the complex cellular composition of glioma and other brain tumors.
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