<i>Sox9</i> prevents retinal degeneration and is required for limbal stem cell differentiation in the adult mouse eye.

Abstract

<i>Sox9</i> is a transcription factor with multiple roles during development and in adult organ homeostasis. In the adult eye, <i>Sox9</i> expression persists in several cell types, including the retinal pigmented epithelium cells and the Müller glial (MG) cells, as well as in the limbal and corneal basal epithelia. To uncover the role of <i>Sox9</i> in these cell types, we induced the deletion of the gene in adult mice. We found that, after <i>Sox9</i> ablation, mutant mice undergo a severe process of retinal degeneration characterized by the loss of MG cells and complete depletion of the photoreceptors layer. Moreover, by combining single-cell RNA sequencing and <i>Sox9</i> lineage tracing, we found that <i>Sox9</i> is 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 of <i>Sox9</i> positive and negative cells confirmed that the gene is essential for limbal stem cell differentiation. Our results show that <i>Sox9</i> is required for the maintenance of retinal integrity and for limbal stem cell differentiation in the adult mouse eye.