m⁶ A promotes planarian regeneration

Area of Science:

• * Molecular Biology
• * Developmental Biology
• * Regenerative Medicine

Background:

• * Regeneration is the biological process of regrowing damaged tissues or organs.
• * Planarians are ideal models for studying regeneration due to their extensive stem cell populations.
• * RNA N⁶ -methyladenosine (m⁶ A) modification influences stem cell functions but its role in whole-organism regeneration is unclear.

Purpose of the Study:

• * To investigate the role of m⁶ A modification in planarian whole-body regeneration.
• * To identify the molecular mechanisms by which m⁶ A regulates regeneration.

Main Methods:

• * Depletion of the m⁶ A methyltransferase regulatory subunit wtap in planarians.
• * Single-cell RNA sequencing (scRNA-seq) to analyze gene expression changes.
• * Functional rescue experiments by depleting specific m⁶ A-modified transcripts.

Main Results:

• * Depletion of wtap abolished planarian regeneration, impacting cell-cell communication and cell cycle genes.
• * scRNA-seq revealed that wtap knockdown induced neural progenitor-like cells expressing the grn ligand.
• * Depleting grn, cdk9, or cdk7 partially rescued regeneration defects caused by wtap depletion.

Conclusions:

• * m⁶ A modification, regulated by wtap, is essential for planarian whole-organism regeneration.
• * m⁶ A likely controls regeneration by modulating cell communication and cell cycle pathways.
• * Targeting m⁶ A pathways offers potential therapeutic strategies for regenerative medicine.