Description |
To systematically address the question how epigenetic state changes in epithelial cells across adjacent normal colon, colorectal adenomas and colorectal cancer, we performed snATAC-seq (single-nucleus Assay for Transposase Accessible Chromatin using sequencing) on 21,311 cells from 34 adjacent normal colon tissues, 10 colorectal adenoma tissues and 45 colorectal cancer tissues of 34 donors. Comparing to normal epithelial cells, cancer epithelial cells displayed dramatic differences in genome-wide chromatin accessibility and high heterogeneity among patients. The gained and lost open chromatin features in adenoma epithelial cells were still maintained in cancer epithelial cells. Motifs of nuclear receptor TF family distinguished one group of cancer epithelial cells from the others. The nuclear receptor TF motif enriched group was composed of cells from left-side colorectal cancer. This group were more accessible at open chromatin regions involved in positive regulation of cell proliferation, cell migration, angiogenesis and response to hypoxia. Overall, our study not only outlines the chromatin accessibility landscapes of colorectal adenomas and cancer, but also explores the possibility of nuclear receptor TFs serving as biomarkers for colorectal cancer subclassification. |