Redox-Dependent Modulation of Human Liver Progenitor Cell Line Fate
News Release, Redox Medicine 2023 , France – March 6, 2023
Representative microscopic images of confluent HepaRG cells exposed to vehicle (CTRL), 100 μM H2O2, or 1 mM N-acetylcysteine every 24 h for 5 days.
Redox homeostasis is determinant in the modulation of quiescence/self-renewal/differentiation of stem cell lines. Bellanti et al. aimed to define the impact of redox modifications on cell fate in a human hepatic progenitor line.
- To achieve this, the HepaRG cell line, which shows oval ductular bipotent characteristics, was used.
- The impact of redox status on the balance between self-renewal and differentiation of HepaRG cells was investigated using different methodological approaches.
- A bioinformatic analysis initially proved that the trans-differentiation of HepaRG toward bipotent progenitors is associated with changes in redox metabolism.
- They then exposed confluent HepaRG (intermediate differentiation phase) to oxidized (H2O2) or reduced (N-acetylcysteine) extracellular environments, observing that oxidation promotes the acquisition of a mature HepaRG phenotype, while a reduced culture medium stimulates de-differentiation.
- These results were finally confirmed through pharmacological modulation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2), a principal modulator of the antioxidant response, in confluent HepaRG.
NRF2 inhibition led to intracellular pro-oxidative status and HepaRG differentiation, while its activation was associated with low levels of reactive species and de-differentiation. In conclusion, this study shows that both intra- and extracellular redox balance are crucial in the determination of HepaRG fate. The impact of redox status in the differentiation potential of HepaRG cells is significant on the utilization of this cell line in pre-clinical studies.
Image credits: Bellanti et al.
Dr. Francesco Bellanti will be a speaker at #RedoxMedicine2023. This year's conference will keep you updated about the latest redox biology updates and discoveries. Submit a related abstract.
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