Spatiotemporal characterization of a distinct nectin-3+ cell population in the developing and adult mouse retina

Abstract

Abstract While Nectin-3 is a recognized marker for maintaining stem and progenitor “side populations” in non-neural epithelia, its role and distribution within the mammalian retina remain largely uncharacterized. Identifying such rare populations is a critical step toward unlocking the regenerative potential of the retina after injury. This study provides a comprehensive spatiotemporal characterization of Nectin-3 + cells from embryonic development through adulthood. Using fluorescence-activated cell sorting, a distinct Nectin-3 + population was identified across all examined stages, representing 1.27% ± 0.24 of viable cells at E18, peaking at P5 (3.62% ± 0.58), and persisting in the adult retina (1.43% ± 0.14). At this mature stage, triple-positive (Nectin-3 + /CD117 + /Sca-1 + ) cells displayed a robust molecular signature defined by the significant up-regulation of Chx10 , Nestin , Pax6 , Rax , and the RGC marker Rbpms , despite a lack of synaptic transcript ( Syp ) enrichment. Morphological analysis via confocal microscopy demonstrated that Nectin-3 + cells undergo dynamic changes during development. In the adult retina, these cells showed colocalization with RBPMS, while remaining distinct from the Müller glial scaffold. Principal Component Analysis highlighted that adult cells retain transcriptional features typically associated with early development, indicating a specialized neuronal identity that is molecularly distinct from the surrounding retinal environment. By defining this fraction, we provide a practical tool for studying retinal diversity and a foundation for investigating the potential regenerative capacity of these rare cells.