RT Journal
A1 Womersley, Howard J.
A1 Muliaditan, Daniel
A1 DasGupta, Ramanuj
A1 Cheow, Lih Feng
T1 Single-nucleus CUT&RUN elucidates the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression
JF Genome Research 
JO Genome Research 
YR 2025 
FD January 01 
VO 35 
IS 1 
SP 162 
OP 177 
DO 10.1101/gr.279105.124 
UL http://genome.cshlp.org/content/35/1/162.abstract 
AB 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.