m6A is required for resolving planarian stem cell identity

The production of missing cell types is critical for regeneration. Gene expression controls cell production and the acquisition of cellular identity. Here, we report that N⁶-methyladenosine (m6A) regulates cell fate choice and cellular maturation of planarian stem cells. We systematically analyzed the function of different components of the m6A pathway, and mapped 7,600 m6A-enriched sites across the planarian transcriptome. Using scRNAseq and in vivo analysis, we found that the m6A pathway is required for production of new intestine cells and inhibiting the production of aberrant undifferentiated cells throughout the animal. Using systematic computational screening of >1000 planarian gene expression libraries, we found that inhibition of the chromatin modifying complex NuRD had almost indistinguishable consequences, indicating a potential link between m6A and chromatin modifications. Our findings reveal that m6A is critical for planarian stem cell maturation and gene regulation in regeneration and homeostasis.