JMJD1C Ensures Mouse Embryonic Stem Cell Self-Renewal and Somatic Cell Reprogramming through Controlling MicroRNA Expression

Summary The roles of histone demethylases (HDMs) for the establishment and maintenance of pluripotency are incompletely characterized. Here, we show that JmjC-domain-containing protein 1c (JMJD1C), an H3K9 demethylase, is required for mouse embryonic stem cell (ESC) self-renewal. Depletion of Jmjd1c leads to the activation of ERK/MAPK signaling and epithelial-to-mesenchymal transition (EMT) to induce differentiation of ESCs. Inhibition of ERK/MAPK signaling rescues the differentiation phenotype caused by Jmjd1c depletion. Mechanistically, JMJD1C, with the help of pluripotency factor KLF4, maintains ESC identity at least in part by regulating the expression of the miR-200 family and miR-290/295 cluster to suppress the ERK/MAPK signaling and EMT. Additionally, we uncover that JMJD1C ensures efficient generation and maintenance of induced pluripotent stem cells, at least partially through controlling the expression of microRNAs. Collectively, we propose an integrated model of epigenetic and transcriptional control mediated by the H3K9 demethylase for ESC self-renewal and somatic cell reprogramming.
Graphical Abstract
Highlights • JMJD1C is required for the maintenance of ESC identity • Depletion of Jmjd1c leads to the activation of ERK/MAPK signaling and EMT • JMJD1C interplays with KLF4 to activate the expression of miR-200 family • JMJD1C ensures efficient induction of pluripotency partially via miR-200 family
In this article, Jin and colleagues show that JMJD1C is required for mouse ESC self-renewal and efficient somatic cell reprogramming. In ESCs, JMJD1C cooperates with KLF4 to suppress the ERK/MAPK signaling and EMT at least in part through promoting miR-200 family and miR-290/295 cluster expression. Additionally, JMJD1C ensures efficient somatic cell reprogramming partially via the miR-200 family.