Single-nucleus CUT&RUN elucidates the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression

IF 6.2 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genome research Pub Date : 2024-12-02 DOI:10.1101/gr.279105.124

Howard Womersley, Daniel Muliaditan, Ramanuj DasGupta, Lih Feng Cheow

{"title":"Single-nucleus CUT&RUN elucidates the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression","authors":"Howard Womersley, Daniel Muliaditan, Ramanuj DasGupta, Lih Feng Cheow","doi":"10.1101/gr.279105.124","DOIUrl":null,"url":null,"abstract":"Interrogating regulatory epigenetic alterations during tumor progression at the resolution of single cells has remained an understudied area of research. Here we developed a highly sensitive single-nucleus CUT&RUN (snCUT&RUN) assay to profile histone modifications in isogenic primary, metastatic, and cisplatin-resistant head and neck squamous cell carcinoma (HNSCC) patient-derived tumor cell lines. We find that the epigenome can be involved in diverse modes to contribute towards HNSCC progression. First, we demonstrate that gene expression changes during HNSCC progression can be comodulated by alterations in both copy number and chromatin activity, driving epigenetic rewiring of cell states. Furthermore, intratumour epigenetic heterogeneity (ITeH) may predispose subclonal populations within the primary tumour to adapt to selective pressures and foster the acquisition of malignant characteristics. In conclusion, snCUT&RUN serves as a valuable addition to the existing toolkit of single-cell epigenomic assays and can be used to dissect the functionality of the epigenome during cancer progression.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"13 1","pages":""},"PeriodicalIF":6.2000,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genome research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1101/gr.279105.124","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Interrogating regulatory epigenetic alterations during tumor progression at the resolution of single cells has remained an understudied area of research. Here we developed a highly sensitive single-nucleus CUT&RUN (snCUT&RUN) assay to profile histone modifications in isogenic primary, metastatic, and cisplatin-resistant head and neck squamous cell carcinoma (HNSCC) patient-derived tumor cell lines. We find that the epigenome can be involved in diverse modes to contribute towards HNSCC progression. First, we demonstrate that gene expression changes during HNSCC progression can be comodulated by alterations in both copy number and chromatin activity, driving epigenetic rewiring of cell states. Furthermore, intratumour epigenetic heterogeneity (ITeH) may predispose subclonal populations within the primary tumour to adapt to selective pressures and foster the acquisition of malignant characteristics. In conclusion, snCUT&RUN serves as a valuable addition to the existing toolkit of single-cell epigenomic assays and can be used to dissect the functionality of the epigenome during cancer progression.

查看原文本刊更多论文

单核CUT&RUN阐明了内在和基因组学驱动的表观遗传异质性在头颈癌进展中的作用

在肿瘤进展过程中，单细胞分辨率下的调控表观遗传改变仍然是一个研究不足的研究领域。在这里，我们开发了一种高度敏感的单核CUT&；RUN （snCUT&；RUN）检测，以分析等基因原发性、转移性和顺铂耐药头颈部鳞状细胞癌（HNSCC）患者来源的肿瘤细胞系中的组蛋白修饰。我们发现表观基因组可以参与多种模式，促进HNSCC的进展。首先，我们证明了HNSCC进展过程中的基因表达变化可以通过拷贝数和染色质活性的改变来调节，从而驱动细胞状态的表观遗传重新连接。此外，肿瘤内表观遗传异质性（ITeH）可能使原发肿瘤内的亚克隆群体倾向于适应选择压力并促进恶性特征的获得。总之，snCUT&；RUN是对现有单细胞表观基因组分析工具包的一个有价值的补充，可用于分析癌症进展过程中表观基因组的功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Genome research 生物-生化与分子生物学

CiteScore

12.40

自引率

1.40%

发文量

140

审稿时长

6 months

期刊介绍： Launched in 1995, Genome Research is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies. New data in these areas are published as research papers, or methods and resource reports that provide novel information on technologies or tools that will be of interest to a broad readership. Complete data sets are presented electronically on the journal''s web site where appropriate. The journal also provides Reviews, Perspectives, and Insight/Outlook articles, which present commentary on the latest advances published both here and elsewhere, placing such progress in its broader biological context.