Comprehensive analysis of partial methylation domains in colorectal cancer based on single-cell methylation profiles

Epigenetic aberrations have played a significant role in affecting the pathophysiological state of colorectal cancer, and global DNA hypomethylation mainly occurs in partial methylation domains (PMDs). However, the distribution of PMDs in individual cells and the heterogeneity between cells are still unclear. In this study, the DNA methylation profiles of colorectal cancer detected by WGBS and scBS-seq were used to depict PMDs in individual cells for the first time. We found that more than half of the entire genome is covered by PMDs. Three subclasses of PMDS have distinct characteristics, and Gain-PMDs cover a higher proportion of protein coding genes. Gain-PMDs have extensive epigenetic heterogeneity between different cells of the same tumor, and the DNA methylation in cells is affected by the tumor microenvironment. In addition, abnormally elevated promoter methylation in Gain-PMDs may further promote the growth, proliferation and metastasis of tumor cells through silent transcription. The PMDs detected in this study have the potential as epigenetic biomarkers and provide a new insight for colorectal cancer research based on single-cell methylation data.