PUBLICATION

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

Authors
Ye, A., Yu, S., Du, M., Zhou, D., He, J., Chen, C.
ID
ZDB-PUB-260122-1
Date
2026
Source
eLIFE   14: (Journal)
Registered Authors
He, Jie
Keywords
Müller glia, cell-cycle re-entry, cxcl18b, neuroscience, nitric oxide, precision redox, zebrafish, zebrafish retina
MeSH Terms
  • Animals
  • Cell Cycle*
  • Cell Proliferation
  • Chemokines, CXC*/genetics
  • Chemokines, CXC*/metabolism
  • Ependymoglial Cells*/metabolism
  • Ependymoglial Cells*/physiology
  • Nitric Oxide*/metabolism
  • Retina*/injuries
  • Retina*/metabolism
  • Zebrafish*
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
PubMed
41562588 Full text @ Elife
Abstract
In lower vertebrates, retinal Müller 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 toward 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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