Bi-compartmentalized stem cell organization of the corneal limbal niche

Abstract

Stem cells exist in precise locations within tissues, yet how their organization supports tissue architecture and function is poorly understood. The limbus is the presumptive stem cell niche of the corneal epithelium. Here, we visualize the live limbus and track the activity of single stem cells in their native environment by 2-photon microscopy. We identify previously unknown niche compartments and show that long implicated slow-cycling cells form separate lineages in the outer limbus, with only local clonal dynamics. Instead, we find distinct stem cells in the pericorneal limbus to be required for corneal regeneration. Unbiased photolabeling captures their progeny exiting the niche, then moving centripetally in unison before undergoing terminal differentiation. This study demonstrates how a compartmentalized stem cell organization coordinates tissue regeneration.One Sentence SummaryIn vivo live imaging of the regenerating cornea reveals distinct stem cell activities in the limbal niche

Three-Dimensional Imaging in Stem Cell-Based Researches

“…However, due to the longer wavelengths, the optical resolution is lower than the confocal system. The two-photon microscopy could be useful to visualize collagen-enriched bone or tooth structures after hard tissue clearing (147,148), 3D imaging of corneal stem cells in mouse eye (149), imaging of 3D stem cell spheroids (150) and even intracutaneous imaging of stem cell activity in a live mice (151).…”