TY - JOUR
T1 - PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells
AU - Yamaji, Masashi
AU - Ueda, Jun
AU - Hayashi, Katsuhiko
AU - Ohta, Hiroshi
AU - Yabuta, Yukihiro
AU - Kurimoto, Kazuki
AU - Nakato, Ryuichiro
AU - Yamada, Yasuhiro
AU - Shirahige, Katsuhiko
AU - Saitou, Mitinori
N1 - Funding Information:
We are grateful to S. Yamanaka and M. Koyanagi for the anti-DNMT3L antibody, H. Kimura for the anti-H3K27Ac antibody, H. Niwa for the pBRPyCAG and pPyCAG-IRESneo/pac plasmids, M. Okano for the Dnmt3a2 and Dnmt3b1 expression plasmids and Dnmt TKO ESCs, K. Hata for the Dnmt3l expression plasmid, M.S.H. Ko for the Tcl1 expression plasmid, Y. Katou and S. Fukuzawa for assistance, and I. Oinuma and H. Harada for their comments and suggestions. We also thank R. Kabata, S. Ohsako, N. Konishi, K. Nakagawa, and K. Osugi for assistance. The authors were supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, by JST-CREST/ERATO, by the Takeda Science Foundation, by the Uehara Memorial Foundation, and by the Mitsubishi Foundation.
PY - 2013/3/7
Y1 - 2013/3/7
N2 - In serum, mouse embryonic stem cells (mESCs) fluctuate between a naive inner cell mass (ICM)-like state and a primed epiblast-like state, but when cultured with inhibitors of the mitogen-activated protein kinase (MAPK) and glycogen synthase kinase 3 pathways (2i), they are harnessed exclusively in a distinct naive pluropotent state, the ground state, that more faithfully recapitulates the ICM. Understanding the mechanism underlying this naive pluripotent state will be critical for realizing the full potential of ESCs. We show here that PRDM14, a PR-domain-containing transcriptional regulator, ensures naive pluripotency through a dual mechanism: antagonizing activation of the fibroblast growth factor receptor (FGFR) signaling by the core pluripotency transcriptional circuitry, and repressing expression of de novo DNA methyltransferases that modify the epigenome to a primed epiblast-like state. PRDM14 exerts these effects by recruiting polycomb repressive complex 2 (PRC2) specifically to key targets and repressing their expression.
AB - In serum, mouse embryonic stem cells (mESCs) fluctuate between a naive inner cell mass (ICM)-like state and a primed epiblast-like state, but when cultured with inhibitors of the mitogen-activated protein kinase (MAPK) and glycogen synthase kinase 3 pathways (2i), they are harnessed exclusively in a distinct naive pluropotent state, the ground state, that more faithfully recapitulates the ICM. Understanding the mechanism underlying this naive pluripotent state will be critical for realizing the full potential of ESCs. We show here that PRDM14, a PR-domain-containing transcriptional regulator, ensures naive pluripotency through a dual mechanism: antagonizing activation of the fibroblast growth factor receptor (FGFR) signaling by the core pluripotency transcriptional circuitry, and repressing expression of de novo DNA methyltransferases that modify the epigenome to a primed epiblast-like state. PRDM14 exerts these effects by recruiting polycomb repressive complex 2 (PRC2) specifically to key targets and repressing their expression.
UR - http://www.scopus.com/inward/record.url?scp=84875222965&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875222965&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2012.12.012
DO - 10.1016/j.stem.2012.12.012
M3 - Article
C2 - 23333148
AN - SCOPUS:84875222965
SN - 1934-5909
VL - 12
SP - 368
EP - 382
JO - Cell stem cell
JF - Cell stem cell
IS - 3
ER -