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bioRxiv · 10.1101/2025.02.14.638343

cxcl18b-defined transitional state-specific nitric oxide drives injury-induced Müller glia cell-cycle re-entry in the zebrafish retina

Ye, A.·Yu, S.·Du, M.·Zhou, D.·He, J.·Chen, C.
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Abstract

In lower vertebrates, retinal Muller glia (MG) exhibit a life-long capacity of cell-cycle re-entry to regenerate neurons following the retinal injury. However, the mechanism driving such injury-induced MG cell-cycle re-entry remains incompletely understood. Combining single-cell transcriptomic analysis and in-vivo clonal analysis, we identified previously undescribed cxcl18b-defined MG transitional states as essential routes towards MG proliferation following green/red cone (G/R cone) ablation. Inflammation blockage abolished the triggering of these transitional states, which expressed the gene modules shared by cells of the ciliary marginal zone (CMZ), where life-long adult neurogenesis takes place. Functional studies of the redox properties of these transitional states further demonstrated the regulatory role of nitric oxide (NO) produced by Nos2b in injury-induced MG proliferation. Finally, we developed a viral-based strategy to specifically disrupt nos2b in cxcl18b-defined MG transitional states and revealed the effect of transitional state-specific NO signaling. Our findings elucidate the precision redox mechanism underlying injury-induced MG cell-cycle re-entry, providing insights into species-specific mechanisms for vertebrate retina regeneration.

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Ye, A., Yu, S., Du, M., Zhou, D., He, J., Chen, C.. 2025-02-17. cxcl18b-defined transitional state-specific nitric oxide drives injury-induced Müller glia cell-cycle re-entry in the zebrafish retina. https://doi.org/10.1101/2025.02.14.638343

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