m6A Modification Regulates Planarian Regeneration [MeRIP-seq]

The fundamental of regeneration process of invertebrates involves the renewal, differentiation and reprogramming of stem cell in an orchestrated manner. It has been known that N6-methyladenosine (m6A) regulates stem cell renewal and differentiation. It is still unclear if m6A is crucial for the regeneration at whole-organism level. Here, we demonstrate that wtap knockdown mediated m6A depletion impairs planarian regeneration upon amputation. The cell cycle related genes displayed decreased m6A while increased expression levels in response to wtap knockdown. The m6A depletion induced phenotypes can be rescued by double-knocking down these genes together with wtap, suggesting that m6A-mediated cell cycle controls planarian regeneration. Further analysis combining the single-cell sequencing unveils a unique neuronal progenitor-like cell type, named NCC and characterized by specific expression of grn, which is indispensable for neuroregeneration. Overall, our study uncovered an essential role of wtap-mediated m6A modification in regulating stem cell population dynamics and homeostasis in terms of general-body regeneration. Overall design: MeRIP-seq of 15 samples from planarian at 0 hpa, 6 hpa, 3 dpa, 7 dpa and 11 dpa, and 15 samples from wtap knockdown planarian at 0 hpa, 6 hpa, 3 dpa, 7 dpa and 11 dpa, including three biological replicates.