Prdm14 promotes mouse ESC self-renewal and PGCLC specification through enhancement of Stat3 activity

Prdm14 plays an important role in the maintenance of mouse embryonic stem cell (mESC) pluripotency and the specification of primordial germ cells (PGCs). However, the mechanism downstream of Prdm14 is still not fully understood. Here, using high-throughput sequencing, chromatin immunoprecipitation, and luciferase reporter assays, we show that Prdm14 directly binds to the promoter of Socs3 and represses its transcription to increase the phosphorylation level of Stat3 protein, a critical downstream effector of LIF. Therefore, ectopic expression of Socs3 is able to decrease the ability of Prdm14 to promote mouse mESC self-renewal and PGC-like cell generation. As expected, similar phenotypes were observed in Prdm14-transfected mESCs after knockdown of Stat3 transcripts or treatment with a pan-inhibitor of JAKs, positive modulators of the LIF/Stat3 signaling pathway. These data will facilitate a better understanding of the regulatory network governing ESC identity and germ cell development. [Display omitted] •Prdm14 increases the phosphorylation of Stat3 by decreasing Socs3 transcription•Socs3 upregulation impairs Prdm14-mediated ESC maintenance and PGCLC formation•Stat3 inhibition represses Prdm14-mediated ESC self-renewal and PGCLC specification Biological sciences; Cell biology; Stem cells research