Single-nucleus CUT&RUN elucidates the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression
- 1Institute for Health Innovation and Technology, National University of Singapore, Singapore 117599, Singapore;
- 2Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117583, Singapore;
- 3Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore 138672, Singapore
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↵4 These authors contributed equally to this work.
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 toward 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, intratumor epigenetic heterogeneity (ITeH) may predispose subclonal populations within the primary tumor 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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.279105.124.
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Freely available online through the Genome Research Open Access option.
- Received February 14, 2024.
- Accepted November 25, 2024.
This article, published in Genome Research is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
