Sox9prevents retinal degeneration and is required for limbal stem cell differentiation in the adult mouse eye

Sox9is a transcription factor with multiple roles during development and in adult organ homeostasis. In the adult eye,Sox9expression persists in several cell types, including the retinal pigmented epithelium cells and the Müller glial cells, as well as in the limbal and corneal basal epithelia. To uncover the role ofSox9in these cell types, we induced the deletion of the gene in adult mice. We found that, afterSox9ablation, mutant mice undergo a severe process of retinal degeneration characterized by the loss of Müller glial cells and complete depletion of the photoreceptors layer. Moreover, by combining single-cell RNA sequencing andSox9lineage tracing, we found thatSox9is expressed in a basal limbal stem cell population with the ability to form two types of long-lived cell clones involved in stem cell maintenance and homeostasis. Mosaic analysis ofSox9positive and negative cells confirmed that the gene is essential for limbal stem cell differentiation. Our results show thatSox9is required for the maintenance of retinal integrity and for limbal stem cell differentiation in the adult mouse eye.