美国贝勒医学院Akdes Serin Harmanci等研究人员合作发现，单细胞的整合电生理和基因组分析揭示人类胶质瘤中的脉冲放电肿瘤细胞。2024年9月5日出版的《癌细胞》发表了这项成果。

研究人员表示，先前的研究描述了胶质瘤细胞与神经元之间复杂的相互作用，但胶质瘤细胞的内源电生理特性仍不清楚。

为了解决这一问题，研究人员对人类胶质瘤标本进行Patch测序（Patch-seq），发现IDH突变（IDH^mut）肿瘤中三分之一的Patch细胞表现出神经元和胶质细胞的特性。

为了定义这些能触发单个、短促动作电位的混合细胞（HC），并辨别它们是否来源于肿瘤，研究人员开发了单细胞规则关联挖掘（SCRAM）计算工具，以逐一注释每个细胞。

SCRAM揭示了HC具备GABA能神经元和少突胶质前体细胞的选择性特征，包括肿瘤细胞和非肿瘤细胞。

这些研究表征了人类胶质瘤细胞的电生理和分子特性，并描述了一种具有独特电生理和转录组特性的人类胶质瘤细胞类型，这类细胞可能也存在于非肿瘤大脑中。

附：英文原文

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

Author: 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

Issue&Volume: 2024-09-05

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 (IDHmut) 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.

DOI: 10.1016/j.ccell.2024.08.009

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00308-8