Skip to main content
Publications of the Week

Developmental Changes in the Accessible Chromatin, Transcriptome and Ascl1-Binding Correlate with the Loss in Müller Glial Regenerative Potential

By August 21, 2020No Comments

Read the Publication

This week we profile a recent publication in Scientific Reports from the laboratory of
Dr. Thomas Reh (pictured, right) at UW. This study was the PhD thesis work of Leah VandenBosch (pictured, left).

Can you provide a brief overview of your lab’s current research focus?

Our lab is focused on stimulating the regeneration of new neurons in the retina after they have been lost from disease or trauma. In fish, retinal neurons are spontaneously regenerated from glial cells, but in mammals, like ourselves, no neurons or photoreceptors (rods and cones) are made after we are born. To stimulate regeneration of new neurons and photoreceptors in mice, we found that a transcription factor, called Ascl1, will induce mouse glial cells to make some types of retinal neurons, but not all types of neurons can be regenerated in mice.

What is the significance of the findings in this publication?

Some types of neurons can be regenerated in mice by expressing the proneural transcription factor Ascl1, but other types cannot. Specifically, the rod photoreceptor cells, which degenerate in inherited retinal disease, are not regenerated by expressing Ascl1 in the glia. Previous work in our lab implicated epigenetic factors, and in particular histone deacetylation, in limiting neural regeneration from glia. We therefore compared the epigenetic profile of glial cells with retinal progenitors, cells from newborn mice that have the capacity to generate photoreceptors. Using ATACseq and RNAseq, we found distinct epigenetic changes between progenitors and glia that may underlie the loss in the ability of glia to regenerate photoreceptors.

What are the next steps for this research?

Future studies are aimed at trying to rewire the epigenome of glia to be more like that of progenitors. We hope that specific epigenetic reprogramming will open up the possibility of the glia to regenerate photoreceptors in the future, and provide a new way to restore vision to people who are blind from retinal degeneration.

This work was funded by:

The National Eye Institute and the Foundation Fighting Blindness.

Read the Publication