Gene expression data of human normal colon organoids stimulated by IL-17A

With aging, normal human tissues experience expansion of somatic clones that carry cancer mutations. However, whether such clonal expansion exists in the non-neoplastic intestine remains unknown. Here, from whole exome sequencing of 76 clonal human colon organoids, we identify a unique pattern of somatic mutagenesis in the inflamed epithelium of ulcerative colitis patients. The affected epithelium accumulates somatic mutations in multiple IL-17 signaling-related genes, including NFKBIZ, ZC3H12A, and PIGR, which are rarely identified in colon cancer. Targeted sequencing validates pervasive spread of IL-17 signaling-related mutations. Unbiased CRISPR-based knockout screening in colon organoids illuminates mutation-mediated resistance to IL-17A-induced proapoptotic response. Some of these genetic mutations are known to exacerbate experimental colitis in mice, and somatic mutagenesis in human colon epithelium may be causally linked to the inflammatory process. Our findings highlight a unique genetic landscape adapting to a hostile microenvironment and its potential contribution to the pathogenesis of ulcerative colitis. WT and NFKBIZ-KO organoids generated from 2 human normal colon organoids were stimulated by IL-17A. mRNA were extracted from organoids and hybridized to GeneChip PrimeView Human Gene Expression Array, and scanned using GeneChip Scanner 3000 7G.