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

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Integrated electrophysiological and genomic profiles of single cells reveal spiking tumor cells in human glioma
Cancer Cell ( IF 48.8 ) Pub Date : 2024-09-05 , DOI: 10.1016/j.ccell.2024.08.009
Rachel N Curry ₁ , Qianqian Ma ₂ , Malcolm F McDonald ₃ , Yeunjung Ko ₄ , Snigdha Srivastava ₅ , Pey-Shyuan Chin ₆ , Peihao He ₇ , Brittney Lozzi ₈ , Prazwal Athukuri ₉ , Junzhan Jing ₂ , Su Wang ₉ , Arif O Harmanci ₁₀ , Benjamin Arenkiel ₁₁ , Xiaolong Jiang ₁₂ , Benjamin Deneen ₁₃ , Ganesh Rao ₁₄ , Akdes Serin Harmanci ₁₄

Affiliation

The Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA; Program in Development, Disease Models, and Therapeutics, Baylor College of Medicine, Houston, TX, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA; Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX, USA.
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA; Program in Cancer Cell Biology, Baylor College of Medicine, Houston, TX, USA.
Program in Genetics and Genomics, Baylor College of Medicine, Houston, TX, USA.
Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
McWilliams School of Biomedical Informatics, University of Texas Health Science Center, Houston, TX, USA.
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX, USA.
Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
The Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Program in Development, Disease Models, and Therapeutics, Baylor College of Medicine, Houston, TX, USA; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA; Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA; Program in Cancer Cell Biology, Baylor College of Medicine, Houston, TX, USA.
Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA; Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.

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^mut) 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.

中文翻译：

单细胞的综合电生理学和基因组图谱揭示了人神经胶质瘤中的刺突肿瘤细胞

先前的研究描述了神经胶质瘤细胞和神经元之间存在的复杂相互作用;然而，神经胶质瘤细胞内源性的电生理特性仍然不清楚。为了解决这个问题，我们对人神经胶质瘤标本进行了斑片测序（Patch-seq），发现 IDH 突变体（IDH^mut）肿瘤中三分之一的斑片细胞表现出神经元和神经胶质细胞的特性。为了定义这些激发单个短动作电位的杂交细胞（HCs），并辨别它们是否起源于肿瘤，我们开发了单细胞规则关联挖掘（SCRAM）计算工具来单独注释每个细胞。SCRAM 显示 HCs 具有 GABA 能神经元和少突胶质细胞前体细胞的选择特征，包括肿瘤细胞和非肿瘤细胞。这些研究表征了人神经胶质瘤细胞的电生理学和分子特性，并描述了人神经胶质瘤中一种具有独特电生理和转录组特性的细胞类型，该细胞类型也可能存在于非肿瘤大脑中。

更新日期：2024-09-05

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