Genome-wide DNA methylation profiling of CD44low/SSEA-4high and CD44high/SSEA-4low populations in radiation-resistant colorectal cancer organoids

Radiotherapy resistance and post-irradiation tumor regrowth remain major clinical problems in colorectal cancer (CRC), but the residual cellular states that survive irradiation are not well defined. In this study, we established radiation-resistant (RT-R) patient-derived CRC organoid models through repeated irradiation and identified two major populations by flow cytometry: CD44high/SSEA-4low cells and CD44low/SSEA-4high cells. To characterize the epigenetic features of an irradiation-associated persister population, we performed genome-wide DNA methylation profiling using the Infinium MethylationEPIC BeadChip on flow-sorted CD44low/SSEA-4high and CD44high/SSEA-4low populations from RT-R organoids (603iCC), together with whole parental 603iCC organoids. The CD44low/SSEA-4high population showed global hypomethylation relative to the CD44high/SSEA-4low population, and genes showing both hypomethylation within the transcription start site (TSS) 1500 region and upregulation in the matched RNA-seq data were enriched in pluripotency- and differentiation-related pathways, including Hippo and Wnt signaling. These data characterize the epigenetic features of an irradiation-associated CD44low/SSEA-4high persister state in RT-R CRC organoids. Raw IDAT files are not available for this dataset; processed beta value matrices are deposited.