佐瀬 美和子

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 cell derivatives contained radioresistant intestinal stem cells (ISCs) crucial for epithelial regeneration in the damaged intestine after irradiation. Single-cell qRT-PCR analysis showed that surviving Lgr5-expressing cell derivatives in the damaged intestine are remarkably heterogeneous, and that the expression levels of a YAP-target gene Sca1 were inversely correlated with their "stemness", suggesting that the YAP/Wnt signal balance in surviving crypt epithelial cells determines the cellular contribution to epithelial regeneration. Single-cell RNA sequencing of Sca1-Lgr5-derivatives revealed that expression of a tetraspanin family member CD81 correlated well with the expression of ISC- and proliferation-related genes. Consistent with these findings, organoid-forming ability was confined to the CD81hiSca1- fraction within the damaged crypt epithelial cells. Characterization of radioresistant epithelial stem cell heterogeneity in the damaged intestine may contribute to therapeutic strategies for gastrointestinal diseases.

A rare case of acute myelocytic leukemia that relapsed in association with the formation of a gingival tumor is presented. The patient was a 45-year-old man who had been referred to our department for oral examination before starting chemotherapy. No gingival swelling was found on the initial visit. However, about 4 months after complete remission was achieved, he noticed a gingival tumor arising in the left side of the mandible. The tumor was 47 × 32 mm in size and elastic hard, with a relatively well defined border. Pathologically, the lesion was diagnosed as leukemic cell infiltration, despite the hematologic remission. The patient died of respiratory failure about 3 months after presentation, with no response to chemotherapy.