Characterization of radioresistant epithelial stem cell heterogeneity in the damaged mouse intestine

The small intestine has a robust regenerative capacity, and various cell types serve as “cells-of-origin” in the epithelial regeneration process after injury. However, how much each population contributes to regeneration remains unclear. Using lineage tracing, we found that Lgr5-expressing cells' derivatives contained radioresistant ISCs crucial for epithelial regeneration in the damaged intestine after radiation. Single-cell RNA sequencing analysis of Lgr5-derivatives identified primary source of epithelial regeneration in the irradiation damaged intetsine. Overall design: Lgr5-EGFP-Ires-CreERT2: Rosa-lsl-tdTomato mice were injected with tamoxifen at 24 hrs before 10 Gy total body irradiation (TBI). Mice were sacrificed and prepared crypt epithelial cells 48 hrs after TBI. FCM sorted tdTomato+ Sca1- crypt epithelial cells were applied to single cell RNA-seq.