Suwa, Yoshiaki Kwansei Gakuin University
Nishimura, Osamu RIKEN
Sakashita, Nao Kwansei Gakuin University
Kadota, Mitsutaka RIKEN
Nagamatsu, Go Kyushu University
Kawaguchi, Masanori Kwansei Gakuin University
Kashida, Hiroki Kwansei Gakuin University
Nakajima, Ayaka Kwansei Gakuin University
Seki, Yoshiyuki Kwansei Gakuin University
Primordial germ cells (PGCs) are specified from epiblast cells in mice. Genes associated with naive pluripotency are repressed in the transition from inner cell mass to epiblast cells, followed by upregulation after PGC specification. However, the molecular mechanisms underlying the reactivation of pluripotency genes are poorly characterized. Here, we exploited the in vitro differentiation of epiblast-like cells (EpiLCs) from embryonic stem cells (ESCs) to elucidate the molecular and epigenetic functions of PR domain-containing 14 (PRDM14). We found that Prdm14 overexpression in EpiLCs induced their conversion to ESC-like cells even in the absence of leukemia inhibitory factor in adherent culture. This was impaired by the loss of Kruppel-like factor 2 and ten-eleven translocation (TET) proteins. Furthermore, PRDM14 recruited OCT3/4 to the enhancer regions of naive pluripotency genes via TET-base excision repair-mediated demethylation. Our results provide evidence that PRDM14 establishes a transcriptional network for naive pluripotency via active DNA demethylation.
Stem Cell Reports
International Society for Stem Cell Research|Cell Press
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
stemcr_7_6_1072.pdf 2.66 MB