Sep 3, 2019

Cis-Regulatory Accessibility Directs Muller Glial Development and Regenerative Capacity

BioRxiv : the Preprint Server for Biology
Thomas A RehKristen E Cox


Diseases of the retina can lead to losses in neurons and vision. Although the mammalian retina has no inherent regenerative capabilities, fish robustly regenerate from Muller glia (MG). Driving expression of Ascl1 in adult mouse MG stimulates neurogenesis; however, Ascl1-expressing MG primarily generate bipolar cells. To better understand the limits of MG-based regeneration in mouse retinas, we used ATAC- and RNA-seq to compare newborn progenitors with MG. Our analysis demonstrated striking similarities between MG and progenitors, with losses in regulatory motifs for neurogenesis genes. Young MG were found to have intermediate expression profiles and accessible DNA, which is mirrored in the ability of Ascl1 to direct bipolar neurogenesis in young MG. When comparing what makes bipolar and photoreceptor cells distinct from glial cells, we find that bipolar-specific accessible regions are more frequently linked to bHLH motifs and Ascl1 binding, indicating that Ascl1 preferentially binds to bipolar regions. Overall, our analysis indicates a loss of neurogenic gene expression and motif accessibility during glial maturation that may prevent efficient reprogramming.

  • 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

Retinal Bipolar Cells
Nerve Regeneration
Cellular Reprogramming
Binding (Molecular Function)

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 Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.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.