Stem cells have the potential to replace defective cells in several human diseases by depending on their self-renewal and differentiation capacities that are controlled by genes. Currently, exploring the regulation mechanism for stem cell capacities from the perspective of methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine modification has obtained great advance, which functions by regulating target genes post-transcriptionally. However, reviews that interpret the regulatory network of METTL3 in stem cells are still lacking. In this review, we systematically analyze the available publications that report the role and mechanisms of METTL3 in stem cells, including embryonic stem cells, pluripotent stem cells, mesenchymal stem cells, and cancer stem cells. The analysis of such publications suggests that METTL3 controls stem cell fates and is indispensable for maintaining its normal capacities. However, its dysfunction induces various pathologies, particularly cancers. To sum up, this review suggests METTL3 as a key regulator for stem cell capacities, with further exploration potential in translational and clinical fields. In conclusion, this review promotes the understanding of how METTL3 functions in stem cells, which provides a valuable reference for further fundamental studies and clinical applications.
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