Corneal-Committed Cells Restore the Stem Cell Pool and Tissue Boundary following Injury

Abstract

Summary: During morphogenesis, preserving tissue boundaries is essential for cell fate regulation. While embryonic tissues possess high plasticity and repair ability, the questions of whether and how adult tissues cope with acute stem cell (SC) loss or boundary disruption have remained unanswered. Here, we report that K15-GFP transgene labels the murine corneal epithelial boundary and SC niche known as the limbus. K15-GFP+ basal cells expressed SC markers and were located at the corneal regeneration site, as evident by lineage tracing. Remarkably, following surgical deletion of the SC pool, corneal-committed cells dedifferentiated into bona fide limbal SCs that retained normal tissue dynamics and marker expression. Interestingly, however, damage to the limbal stromal niche abolished K15-GFP recovery and led to pathological wound healing. Altogether, this study indicates that committed corneal cells possess plasticity to dedifferentiate, repopulate the SC pool, and correctly re-form the tissue boundary in the presence of intact stroma. : Using a K15-GFP/Confetti transgenic mouse model, Nasser et al. show that the K15-GFP transgene identifies the limbus (i.e., the SC niche and boundary of the corneal epithelium). The authors demonstrate that following SC/boundary depletion, corneal-committed cells dedifferentiate into K15-GFP+ SCs and re-form the tissue boundary in the presence of an intact niche.