Rectal Epithelial Stem Cell Kinetics in Acute Radiation Proctitis

The intestinal tract is a typical radiosensitive tissue, and radiation rectal injury is a severe side effect that limits the prescribed dose in radiotherapy of the abdominal and pelvic region. Understanding the post-irradiation kinetics of <i>Lgr5</i>-positive stem cells is crucial in comprehending this adverse process. In this study, we utilized <i>Lgr5</i>-<i>EGFP</i> knock-in mice expressing EGFP and LGR5 antibody fluorescence staining of wild-type mice. At the state of radiation injury, the qPCR analysis showed a significant decrease in the expression level of <i>Lgr5</i> in the rectal epithelial tissue. The dose-response relationship analysis showed that at low to moderate doses up to 10 gray (Gy), <i>Lgr5</i>-clustered populations were observed at the base of the crypt, whereas at sublethal doses (20 Gy and 29 Gy), the cells exhibited a dot-like scatter pattern, termed <i>Lgr5</i>-dotted populations. During recovery, 30 days post-irradiation, <i>Lgr5</i>-clustered populations gradually re-emerged while <i>Lgr5</i>-dotted populations declined, implying that some of the <i>Lgr5</i>-dotted stem cell populations re-clustered, aiding regenerations. Based on statistical analysis of the dose-response relationship using wild-type mice, the threshold dose for destroying these stem cell structures is 18 Gy. These findings may help set doses in mouse abdominal irradiation experiments for radiation intestinal injury and for understanding the histological process of injury development.