Journal
CELL REPORTS
Volume 30, Issue 7, Pages 2195-2208Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.01.075
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Funding
- Foundation Fighting Blindness [TA-RM-0614-0650-UWA]
- National Institutes of Health (NIH) National Eye Institute (NEI) [1R01EY021482]
- Allen Distinguished Investigator Award (Paul G. Allen Family Foundation)
- National Science Foundation (NSF) Fellowship [DGE-0718124]
- Vision Core grant [P30EY01730]
- NIH NEI Training Grant [EY07031]
- NIH F32 National Research Service Award (NRSA) [5 F32 DC016480-02]
- NIH NEI F31 NRSA [5 F31 EY028412-02]
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Muller glia (MG) serve as sources for retinal regeneration in non-mammalian vertebrates. We find that this process can be induced in mouse MG, after injury, by transgenic expression of the proneural transcription factor Ascl1 and the HDAC inhibitor TSA. However, new neurons are generated only from a subset of MG. Identifying factors that limit Ascl1-mediated MG reprogramming could make this process more efficient. In this study, we test whether injury-induced STAT activation hampers the ability of Ascl1 to reprogram MG into retinal neurons. Single-cell RNA-seq shows that progenitor-like cells derived from Ascl1 expressing MG have a higher level of STAT signaling than do those cells that become neurons. Ascl1-ChIP-seq and ATAC-seq show that STAT potentially directs Ascl1 to developmentally inappropriate targets. 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.
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