Mettl14-driven senescence-associated secretory phenotype facilitates somatic cell reprogramming.

ABSTRACT: The METTL3-METTL14 complex, the "writer" of N⁶-methyladenosine (m⁶A), plays an important role in many biological processes. Previous studies have shown that Mettl3 overexpression can increase the level of m⁶A and promote somatic cell reprogramming. Here, we demonstrate that Mettl14, another component of the methyltransferase complex, can significantly enhance the generation of induced pluripotent stem cells (iPSCs) in an m⁶A-independent manner. In cooperation with Oct4, Sox2, Klf4, and c-Myc, overexpressed Mettl14 transiently promoted senescence-associated secretory phenotype (SASP) gene expression in non-reprogrammed cells in the late stage of reprogramming. Subsequently, we demonstrated that interleukin-6 (IL-6), a component of the SASP, significantly enhanced somatic cell reprogramming. In contrast, blocking the SASP using a senolytic agent or a nuclear factor κB (NF-κB) inhibitor impaired the effect of Mettl14 on reprogramming. Our results highlight the m⁶A-independent function of Mettl14 in reprogramming and provide new insight into the interplay between senescence and reprogramming in vitro.

SUBMITTER: Xi C 

PROVIDER: S-EPMC9391510 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature