Vitamin C and Transferrin Reduce RNA Methylation in Mouse Embryonic Stem Cells

Area of Science:

• Epigenetics and Gene Regulation
• Stem Cell Biology

Background:

• N6-methyladenosine (m⁶A) is the most prevalent internal mRNA modification in eukaryotes, influencing splicing, stability, and translation.
• m⁶A is a reversible modification regulated by specific methylating (Mettl3/Mettl14) and demethylating (FTO/Alkbh5) enzymes.
• Glycogen synthase kinase-3 (Gsk-3) regulates m⁶A levels in mouse embryonic stem cells (ESCs) by controlling FTO demethylase levels.

Approach:

• Investigated the role of small molecules in regulating m⁶A modification and ESC pluripotency.
• Tested the combined effect of Vitamin C and transferrin on m⁶A levels and pluripotency in mouse ESCs.
• Assessed the impact of Gsk-3 inhibition and knockout on FTO protein and m⁶A mRNA levels.

Key Points:

• Glycogen synthase kinase-3 (Gsk-3) activity is a key regulator of m⁶A modification in ESCs, impacting FTO demethylase levels.
• Several small molecules known to promote ESC pluripotency have links to FTO and m⁶A regulation.
• The combination of Vitamin C and transferrin significantly reduces m⁶A levels in mouse ESCs.

Conclusions:

• Vitamin C and transferrin combination effectively promotes the retention of pluripotency in mouse ESCs.
• This combination represents a valuable tool for the culture and maintenance of pluripotent mouse ESCs.
• Understanding the regulation of m⁶A is crucial for stem cell biology and regenerative medicine.