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Common and divergent gene regulatory networks control injury-induced and developmental neurogenesis in zebrafish retina

Pin Lyu, Maria Iribarne, Dmitri Serjanov, Yijie Zhai, Thanh Hoang, Leah J. Campbell, Patrick Boyd, Isabella Palazzo, Mikiko Nagashima, Nicholas J. Silva, Peter F. Hitchcock, Jiang Qian (), David R. Hyde () and Seth Blackshaw ()
Additional contact information
Pin Lyu: Johns Hopkins University School of Medicine
Maria Iribarne: University of Notre Dame
Dmitri Serjanov: University of Notre Dame
Yijie Zhai: Johns Hopkins University School of Medicine
Thanh Hoang: Johns Hopkins University School of Medicine
Leah J. Campbell: University of Notre Dame
Patrick Boyd: University of Notre Dame
Isabella Palazzo: Johns Hopkins University School of Medicine
Mikiko Nagashima: University of Michigan School of Medicine
Nicholas J. Silva: University of Michigan School of Medicine
Peter F. Hitchcock: University of Michigan School of Medicine
Jiang Qian: Johns Hopkins University School of Medicine
David R. Hyde: University of Notre Dame
Seth Blackshaw: Johns Hopkins University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-21

Abstract: Abstract Following acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes through Müller glia (MG) reprogramming and asymmetric cell division that produces a multipotent Müller glia-derived neuronal progenitor cell (MGPC). This raises three key questions. First, do MG reprogram to a developmental retinal progenitor cell (RPC) state? Second, to what extent does regeneration recapitulate retinal development? And finally, does loss of different retinal cell subtypes induce unique MG regeneration responses? We examined these questions by performing single-nuclear and single-cell RNA-Seq and ATAC-Seq in both developing and regenerating retinas. Here we show that injury induces MG to reprogram to a state similar to late-stage RPCs. However, there are major transcriptional differences between MGPCs and RPCs, as well as major transcriptional differences between activated MG and MGPCs when different retinal cell subtypes are damaged. Validation of candidate genes confirmed that loss of different subtypes induces differences in transcription factor gene expression and regeneration outcomes.

Date: 2023
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DOI: 10.1038/s41467-023-44142-w

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