Positive feedback between retinoic acid and 2-phospho-L-ascorbic acid trisodium salt during somatic cell...

Area of Science:

• Stem cell biology
• Molecular biology
• Biochemistry

Background:

• Retinoic acid (RA) and 2-phospho-L-ascorbic acid trisodium salt (AscPNa) are known to promote induced pluripotent stem cell (iPSC) generation.
• The combined effects and potential interactions of RA and AscPNa in reprogramming are not fully understood.

Purpose of the Study:

• To investigate the interplay between RA and AscPNa during mouse embryonic fibroblast reprogramming.
• To elucidate the molecular mechanisms underlying their synergistic or antagonistic effects.

Main Methods:

• RNA sequencing (RNA-seq) to analyze gene expression overlap.
• Analysis of molecular pathways involved in mesenchymal-epithelial transition (MET).
• Assessment of intracellular vitamin A and C levels.

Main Results:

• RA and AscPNa share partially overlapping downstream pathways during reprogramming.
• RA enhances dehydroascorbic acid transport, increasing intracellular L-ascorbic acid levels.
• AscPNa promotes MET, downregulates RA-metabolizing enzymes (Cyp26a1/b1), and sustains intracellular RA levels.
• A positive feedback loop between RA and AscPNa was identified.

Conclusions:

• RA and AscPNa exhibit complex interactions, including a positive feedback mechanism, during cell reprogramming.
• Understanding these interactions is crucial for optimizing reprogramming protocols and exploring the roles of vitamins A and C in cellular plasticity.