ZFIN ID: ZDB-PUB-190611-3
Redox Signaling via Lipid Peroxidation Regulates Retinal Progenitor Cell Differentiation
Albadri, S., Naso, F., Thauvin, M., Gauron, C., Parolin, C., Duroure, K., Vougny, J., Fiori, J., Boga, C., Vriz, S., Calonghi, N., Del Bene, F.
Date: 2019
Source: Developmental Cell   50(1): 73-89.e6 (Journal)
Registered Authors: Albadri, Shahad, Del Bene, Filippo, Duroure, Karine, Gauron, Carole, Vriz, Sophie
Keywords: 9-hydroxystearic acid, H(2)O(2), HDAC1, lipid peroxidation, neuronal differentiation, redox signaling, retinal progenitor cells, stem cell metabolism, zebrafish
MeSH Terms:
  • Animals
  • Cell Differentiation*
  • Cell Proliferation
  • Histone Deacetylase 1/genetics
  • Histone Deacetylase 1/metabolism
  • Lipid Peroxidation*
  • Neurogenesis*
  • Oxidation-Reduction
  • Reactive Oxygen Species/metabolism*
  • Retina/cytology*
  • Retina/physiology
  • Stem Cells/cytology*
  • Stem Cells/physiology
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 31178398 Full text @ Dev. Cell
Reactive oxygen species (ROS) and downstream products of lipid oxidation are emerging as important secondary messengers in tissue homeostasis. However, their regulation and mechanism of action remain poorly studied in vivo during normal development. Here, we reveal that the fine regulation of hydrogen peroxide (H2O2) levels by its scavenger Catalase to mediate the switch from proliferation to differentiation in retinal progenitor cells (RPCs) is crucial. We identify 9-hydroxystearic acid (9-HSA), an endogenous downstream lipid peroxidation product, as a mediator of this effect in the zebrafish retina. We show that the 9-HSA proliferative effect is due to the activation of Notch and Wnt pathways through the inhibition of the histone deacetylase 1. We show that the local and temporal manipulation of H2O2 levels in RPCs is sufficient to trigger their premature differentiation. We finally propose a mechanism that links H2O2 homeostasis and neuronal differentiation via the modulation of lipid peroxidation.