A robust transcriptional program in newts undergoing multiple events of lens regeneration throughout their lifespan

Abstract

Newts have the ability to repeatedly regenerate their lens even during ageing. However, it is unclear whether this regeneration reflects an undisturbed genetic activity. To answer this question, we compared the transcriptomes of lenses, irises and tails from aged newts that had undergone lens regeneration 19 times with the equivalent tissues from young newts that had never experienced lens regeneration. Our analysis indicates that repeatedly regenerated lenses showed a robust transcriptional program comparable to young never-regenerated lenses. In contrast, the tail, which was never regenerated, showed gene expression signatures of ageing. Our analysis strongly suggests that, with respect to gene expression, the regenerated lenses have not deviated from a robust transcriptional program even after multiple events of regeneration throughout the life of the newt. In addition, our study provides a new paradigm in biology, and establishes the newt as a key model for the study of regeneration in relation to ageing.Newts are unusual animals because they are able to regenerate injured or lost body parts. To regenerate the lens in an eye, certain cells in the iris need to change into lens cells. In 2011, a group of researchers reported the results of a 16-year long study of lens regeneration in Japanese newts. This study found that lenses from old newts that have undergone lens regeneration many times are structurally identical to those of young individuals that still have their original lenses. Also, many genes required to make lens proteins were expressed at similar levels in the lenses of the old and young newts. Therefore, even old newts retain the ability to fully regenerate their lenses.However, it is possible that the lenses in the old newts might show more subtle signs of ageing in the form of differences in the expression of other genes. Here, Sousounis et al. – including some of the researchers from the 2011 work – used an approach called transcriptomics to examine the patterns of gene expression in this group of newts in more detail.Sousounis et al. collected cells from the lenses, irises and tails of both the old and young newts. The experiments show that the patterns of gene expression in the regenerated lenses closely resemble the patterns seen in the lenses of the young newts. In contrast, the tail cells of the old and young newts display different gene expression patterns, with those from the older newts displaying hallmarks of ageing that are absent in the younger newts. The iris cells from the old newts show a mixed gene expression profile with features characteristic of both young and aged tissue. Sousounis et al.’s findings highlight the value of using newts as models to study the links between regeneration and ageing