m 6 A promotes planarian regeneration

• Published in: Cell proliferation Vol. 56; no. 5; p. e13481
• Main Authors: Cui, Guanshen, Zhou, Jia-Yi, Ge, Xin-Yang, Sun, Bao-Fa, Song, Ge-Ge, Wang, Xing, Wang, Xiu-Zhi, Zhang, Rui, Wang, Hai-Lin, Jing, Qing, Koziol, Magdalena J, Zhao, Yong-Liang, Zeng, An, Zhang, Wei-Qi, Han, Da-Li, Yang, Yun-Gui, Yang, Ying
• Format: Journal Article
• Language: English
• Published: England 01.05.2023
• Subjects: Adult Stem Cells; Animals; Cell Differentiation - genetics; Cell Division; Mammals; Planarians - genetics; Planarians - metabolism; RNA Interference
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/cpr.13481

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 -methyladenosine (m 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 A controls regeneration at the whole-organism level remains largely unknown. Here, we demonstrate that the depletion of m 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 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 A modification in regulating whole-organism regeneration.