单细胞的综合电生理和基因组图谱揭示了人类胶质瘤中的尖峰肿瘤细胞

IF 48.8 1区 医学 Q1 CELL BIOLOGY
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
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引用次数: 0

摘要

先前的研究已经描述了胶质瘤细胞和神经元之间存在的复杂相互作用;然而,胶质瘤细胞的内源性电生理特性仍然不明显。为了解决这个问题,我们在人类胶质瘤标本上采用了补丁测序(Patch-sequencing,Patch-seq)技术,发现IDH突变(IDHmut)肿瘤中有三分之一的补丁细胞同时具有神经元和胶质细胞的特性。为了定义这些能发出单个短动作电位的混合细胞(HCs),并确定它们是否源于肿瘤,我们开发了单细胞规则关联挖掘(SCRAM)计算工具,对每个细胞进行单独注释。SCRAM 发现,HCs 具有 GABA 能神经元和少突胶质细胞前体细胞的特征,包括肿瘤细胞和非肿瘤细胞。这些研究描述了人类胶质瘤细胞的综合电生理学和分子特性,并描述了人类胶质瘤中一种具有独特电生理学和转录组学特性的细胞类型,这种细胞类型可能也存在于非肿瘤大脑中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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.

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来源期刊
Cancer Cell
Cancer Cell 医学-肿瘤学
CiteScore
55.20
自引率
1.20%
发文量
179
审稿时长
4-8 weeks
期刊介绍: Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.
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