Effects of N-myristoyltransferase inhibition on mouse and human pluripotent stem cells

N-myristoyltransferase (Nmt) is an enzyme that catalyzes the addition of a myristoyl group to the N-terminal region of proteins. In mice and humans, there are two Nmt genes, Nmt1 and Nmt2. The expression level of Nmt1 is higher than that of Nmt2 in pluripotent stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Through a recessive genetic screen of a homozygous mutant mouse ESC library, we found that the disruption of Nmt1 confers differentiation resistance to mouse ESCs. To elucidate the role of Nmt in the regulation of pluripotency, we performed bulk RNA-seq on Nmt1-homozygous mutant mouse ESCs and wild-type ESCs, and bulk RNA-seq and single-cell RNA-seq on human iPSCs in the presence and absence of the Nmt inhibitor DDD85646. The results indicate that Nmt is a novel target for the regulation of pluripotency.