Age-dependent Müller glia neurogenic competence in the mouse retina

Glia ◽  
2015 ◽  
Vol 63 (10) ◽  
pp. 1809-1824 ◽  
Author(s):  
Kati Löffler ◽  
Patrick Schäfer ◽  
Manuela Völkner ◽  
Tina Holdt ◽  
Mike O. Karl
Keyword(s):  
Mouse Retina ◽  
Muller Glia ◽  
Müller Glia ◽  
Age Dependent

scholarly journals The circadian clock gene Bmal1 is required to control the timing of retinal neurogenesis and lamination of Müller glia in the mouse retina

2019 ◽  
Vol 33 (8) ◽  
pp. 8745-8758 ◽  
Author(s):  
Onkar B. Sawant ◽  
Vijay K. Jidigam ◽  
Rebecca D. Fuller ◽  
Olivia F. Zucaro ◽  
Cristel Kpegba ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Gene ◽  
Mouse Retina ◽  
Muller Glia ◽  
Müller Glia ◽  
Circadian Clock Gene ◽  
Retinal Neurogenesis

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

2019 ◽  
Author(s):  
Nikolas L. Jorstad ◽  
Matthew S. Wilken ◽  
Levi Todd ◽  
Paul Nakamura ◽  
Nick Radulovich ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Neural Regeneration ◽  
Mouse Retina ◽  
Binding Motif ◽  
Muller Glia ◽  
Müller Glia ◽  
Rna Seq ◽  
Transgenic Expression ◽  
Pathway Activation ◽  
Stat Pathway

AbstractMüller glia can serve as a source for retinal regeneration in some non-mammalian vertebrates. Recently we found that this process can be induced in mouse Müller glia 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 Müller glia 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 Müller glia in response to injury. In this report, we tested whether injury induced STAT activation hampers the ability of Ascl1 to reprogram Müller glia into retinal neurons. Using a STAT inhibitor, in combination with our previously described reprogramming paradigm, we found a large increase in the ability of Müller glia to generate neurons, similar to those we described previously. Single-cell RNA-seq showed that the progenitor-like cells derived from Ascl1-expressing Müller glia 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 sites (that were unique to the overexpression context) had enrichment for the STAT binding motif. This study provides evidence that STAT pathway activation reduces the efficiency of Ascl1-mediated reprogramming in Müller glia, potentially by directing Ascl1 to inappropriate targets.

Pax6-positive müller glia cells express cell cycle markers but do not proliferate after photoreceptor injury in the mouse retina

Glia ◽  
2011 ◽  
Vol 59 (7) ◽  
pp. 1033-1046 ◽  
Author(s):  
Sandrine Joly ◽  
Vincent Pernet ◽  
Marijana Samardzija ◽  
Christian Grimm
Keyword(s):  
Cell Cycle ◽  
Mouse Retina ◽  
Muller Glia ◽  
Müller Glia ◽  
Glia Cells ◽  
Express Cell

scholarly journals Anatomy and spatial organization of Müller glia in mouse retina

2017 ◽  
Vol 525 (8) ◽  
pp. spc1-spc1 ◽  
Author(s):  
Jingjing Wang ◽  
Matthew L. O’Sullivan ◽  
Dibyendu Mukherjee ◽  
Vanessa M. Puñal ◽  
Sina Farsiu ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Mouse Retina ◽  
Muller Glia ◽  
Müller Glia

scholarly journals STAT Signaling Modifies Ascl1 Chromatin Binding and Limits Neural Regeneration from Muller Glia in Adult Mouse Retina

Cell Reports ◽  
2020 ◽  
Vol 30 (7) ◽  
pp. 2195-2208.e5 ◽  
Author(s):  
Nikolas L. Jorstad ◽  
Matthew S. Wilken ◽  
Levi Todd ◽  
Connor Finkbeiner ◽  
Paul Nakamura ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Neural Regeneration ◽  
Mouse Retina ◽  
Muller Glia ◽  
Chromatin Binding ◽  
Müller Glia ◽  
Stat Signaling

scholarly journals mTORC1-induced retinal progenitor cell overproliferation leads to accelerated mitotic aging and degeneration of descendent Müller glia

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Soyeon Lim ◽  
You-Joung Kim ◽  
Sooyeon Park ◽  
Ji-heon Choi ◽  
Younghoon Sung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Tuberous Sclerosis Complex ◽  
Progenitor Cell ◽  
Mouse Retina ◽  
Muller Glia ◽  
Müller Glia ◽  
Retinal Progenitor ◽  
Mechanistic Target Of Rapamycin ◽  
Glycolytic Gene

Retinal progenitor cells (RPCs) divide in limited numbers to generate the cells comprising vertebrate retina. The molecular mechanism that leads RPC to the division limit, however, remains elusive. Here, we find that the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) in an RPC subset by deletion of tuberous sclerosis complex 1 (Tsc1) makes the RPCs arrive at the division limit precociously and produce Müller glia (MG) that degenerate from senescence-associated cell death. We further show the hyperproliferation of Tsc1-deficient RPCs and the degeneration of MG in the mouse retina disappear by concomitant deletion of hypoxia-induced factor 1-a (Hif1a), which induces glycolytic gene expression to support mTORC1-induced RPC proliferation. Collectively, our results suggest that, by having mTORC1 constitutively active, an RPC divides and exhausts mitotic capacity faster than neighboring RPCs, and thus produces retinal cells that degenerate with aging-related changes.

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