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Deciphering the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression with single-nucleus CUT&RUN [single-nucleus CUT&RUN]

ABSTRACT: Single-cell RNA sequencing (scRNA-seq) has proven to be an invaluable tool for the study of tumor evolution. However, interrogating regulatory epigenetic alterations during cancer progression at the resolution of single-cells has remained a major challenge due to the lack of sensitivity of current assays. Here, we developed the highly-sensitive single-nucleus CUT&RUN (snCUT&RUN) assay to profile histone modifications in primary, metastatic, and cisplatin-resistant head and neck squamous cell carcinoma (HNSCC) patient-derived cell lines. We find that the epigenome can employ diverse modes to contribute towards cancer progression. Notably, we demonstrate that gene expression changes during cancer progression are co-modulated by alterations in both copy number and chromatin activity to drive epigenetic rewiring of cell-states. Furthermore, intratumor epigenetic heterogeneity may predispose sub-clonal populations within the primary tumor to acquire malignant characteristics. In conclusion, snCUT&RUN serves as a valuable addition to existing toolkit of single-cell assays to dissect the function of the epigenome during cancer progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE212249 | GEO | 2024/11/18

REPOSITORIES: GEO

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Deciphering the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression with single-nucleus CUT&RUN [bulk RNAseq]

Project description:Single-cell RNA sequencing (scRNA-seq) has proven to be an invaluable tool for the study of tumor evolution. However, interrogating regulatory epigenetic alterations during cancer progression at the resolution of single-cells has remained a major challenge due to the lack of sensitivity of current assays. Here, we developed the highly-sensitive single-nucleus CUT&RUN (snCUT&RUN) assay to profile histone modifications in primary, metastatic, and cisplatin-resistant head and neck squamous cell carcinoma (HNSCC) patient-derived cell lines. We find that the epigenome can employ diverse modes to contribute towards cancer progression. Notably, we demonstrate that gene expression changes during cancer progression are co-modulated by alterations in both copy number and chromatin activity to drive epigenetic rewiring of cell-states. Furthermore, intratumor epigenetic heterogeneity may predispose sub-clonal populations within the primary tumor to acquire malignant characteristics. In conclusion, snCUT&RUN serves as a valuable addition to existing toolkit of single-cell assays to dissect the function of the epigenome during cancer progression.

2024-11-18 | GSE212247 | GEO

Deciphering the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression with single-nucleus CUT&RUN [single-nucleus CUT&RUN]

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Deciphering the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression with single-nucleus CUT&RUN

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Project description:Endosperm is an essential seed tissue with a unique epigenetic landscape. During endosperm development, differential epigenetic regulation of the maternal and paternal genomes plays important roles in regulating gene expression, especially at imprinted genes. Profiling the endosperm epigenetic landscape on a genome-wide scale is challenging due to its small size, mode of development, and close association with maternal tissue. Here, we applied a low input chromatin profiling method, CUT&RUN (cleavage under targets and release using nuclease), to profile parental-specific chromatin modifications using low numbers of Arabidopsis endosperm nuclei. We demonstrate that CUT&RUN generates genome-wide H3K27me3 landscapes with high sensitivity, specificity and reproducibility using around 20,000 endosperm nuclei purified by flow cytometry and fluorescence-activated cell sorting. H3K27me3 peaks identified by CUT&RUN and previous ChIP (chromatin immunoprecipitation) approaches were largely overlapping, with some distinctions in heterochromatin. The versatility and simplicity of CUT&RUN makes it a viable alternative to ChIP, which requires greater amounts of starting material, and will enable the study of tissue or even cell-type specific epigenomes in Arabidopsis and other plant species.

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Deciphering the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression with single-nucleus CUT&RUN [bulk RNAseq]

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