m6A promotes planarian regeneration

Abstract Regeneration is the regrowth of damaged tissues or organs, a vital process in response to damages from primitive organisms to higher mammals. Planarian possesses active whole‐body regenerative capability owing to its vast reservoir of adult stem cells, neoblasts, providing an ideal model to delineate the underlying mechanisms for regeneration. RNA N 6 ‐methyladenosine (m 6 A) modification participates in many biological processes, including stem cell self‐renewal and differentiation, in particular the regeneration of haematopoietic stem cells and axons. However, how m 6 A controls regeneration at the whole‐organism level remains largely unknown. Here, we demonstrate that the depletion of m 6 A methyltransferase regulatory subunit wtap abolishes planarian regeneration, potentially through regulating genes related to cell–cell communication and cell cycle. Single‐cell RNA‐seq (scRNA‐seq) analysis unveils that the wtap knockdown induces a unique type of neural progenitor‐like cells (NP‐like cells), characterized by specific expression of the cell–cell communication ligand grn . Intriguingly, the depletion of m 6 A‐modified transcripts grn , cdk9 or cdk7 partially rescues the defective regeneration of planarian caused by wtap knockdown. Overall, our study reveals an indispensable role of m 6 A modification in regulating whole‐organism regeneration.