Comparative transcriptomic and epigenomic analysis identifes regulators of neurogenic competence in retinal Müller glia.

Abstract

Purpose : A potential approach for restoring vision in patients with photoreceptor dystrophies is the regeneration of lost retinal neurons from Müller glia. To identify molecular mechanisms that control neurogenic competence in Müller glia, we have carried out a large-scale comparative transcriptomic and epigenomic analysis using zebrafish (regeneration-competent), chick (regeneration-limited), and mouse (regeneration-refractory).

Methods : We have used RNA-Seq, miRNA-Seq and ATAC-Seq to comprehensively profile changes in mRNA and miRNA expression, as well as chromatin conformation, that occur during differentiation of Müller glia from retinal progenitor cells, and following both inner and outer retinal damage, as well as growth factor treatment, in all three species.

Results : These data have identified many candidate genes and transcriptional regulatory networks that either promote or restrict neurogenic competence in Müller glia.

Conclusions : These findings may help identify molecular pathways that could be targeted to induce neurogenic competence in human Müller glia.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.