By combining single-cell RNA sequencing analysis, a variety of primary fibroblast and primary intestinal epithelial organoid models, mouse intestinal tissue analysis, transcriptomic studies, and colorectal cancer (CRC) patient cohort survival analyses, we show that NRG1, but not EREG, is sufficient to reprogram the intestinal epithelium into a regenerative, fetal-like state without promoting tumorigenic growth. The gene discussed is EREG; the disease is colorectal carcinoma.