Sep 3, 2019

STAT pathway activation limits the Ascl1-mediated chromatin remodeling required for neural regeneration from Muller glia in adult mouse retina.

BioRxiv : the Preprint Server for Biology
Thomas A RehFred Rieke


Muller glia (MG) can serve as a source for retinal regeneration in some non-mammalian vertebrates. Recently we found that this process can be induced in mouse MG after injury, by combining transgenic expression of the proneural transcription factor Ascl1 and the HDAC inhibitor TSA. However, new neurons are only generated from a subset of MG in this model, and identifying factors that limit Ascl1-mediated MG reprogramming could potentially make this process more efficient, and potentially useful clinically. One factor that limits neurogenesis in some non-mammalian vertebrates is the STAT pathway activation that occurs in MG in response to injury. In this report, we tested whether injury induced STAT activation hampers the ability of Ascl1 to reprogram MG into retinal neurons. Using a STAT inhibitor, in combination with our previously described reprogramming paradigm, we found a large increase in the ability of MG to generate neurons, similar to those we described previously. Single-cell RNA-seq showed that the progenitor-like cells derived from Ascl1-expressing MG have a higher level of STAT signaling than those that become neurons. Using Ascl1 ChIP-seq and DNase-seq, we found that developmentally inappropriate Ascl1 binding sit...Continue Reading

  • References
  • Citations


  • We're still populating references for this paper, please check back later.
  • References
  • Citations


  • This paper may not have been cited yet.

Mentioned in this Paper

Single-Cell Analysis
Plants, Transgenic
Nerve Regeneration
Cellular Reprogramming

About this Paper

Related Feeds


Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Yumi UekiThomas A Reh
Investigative Ophthalmology & Visual Science
Bo LiuJill A Helms
Current Opinion in Genetics & Development
Matthew S Wilken, Thomas A Reh
© 2020 Meta ULC. All rights reserved