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PRDM14 Ensures a Naïve Pluripotency by a Dual Mechanism Involving Signaling and Epigenetic Pathways in Mouse Embryonic Stem Cells

ABSTRACT: Mouse embryonic stem cells (mESCs) fluctuate between a naïve inner cell mass (ICM)-like state and a primed epiblast-like state of pluripotency in serum, but are harnessed exclusively in a distinctive, apparently more naïve state of pluripotency (the ground state) with inhibitors for mitogen-activated protein kinase (MAPK) and glycogen synthase kinase 3 pathways (2i). Understanding the mechanism ensuring a naïve state of pluripotency would be critical in realizing a full potential of ESCs. We show here that PRDM14, a PR domain-containing transcriptional regulator, ensures a naïve pluripotency by a dual mechanism: Antagonizing fibroblast growth factor receptor (FGFR) signaling that is activated paradoxically by the core transcriptional circuitry for pluripotency and directs a primed state and repressing de novo DNA methyltransferases that create a primed epiblast-like epigenome. PRDM14 exerts these functions by recruiting polycomb repressive complex 2 (PRC2) specifically to key targets and repressing their expression. Mouse Embryonic Stem Cells (mESCs) or mESC-like cells with different Prdm14 genotypes {Prdm14(+/+), Prdm14(-/-), and Prdm14(-/-) rescued with Avitag-EGFP-Prdm14 transgene [Prdm14(-/-)+AGP14]} are cultured on MEF in different medium [2i, Serum(day 2), Serum+MEK inhibitor (PD0325901) (day 2), Serum without LIF (day2)].

ORGANISM(S): Mus musculus  

SUBMITTER: Mitinori Saitou   Yasuhiro Yamada  Kazuki Kurimoto  Ryuichiro Nakato  Yukihiro Yabuta  Katsuhiko Shirahige  Hiroshi Ohta  Jun Ueda  Katsuhiko Hayashi  Masashi Yamaji 

PROVIDER: E-GEOD-42580 | ArrayExpress | 2013-01-18



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PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells.

Yamaji Masashi M   Ueda Jun J   Hayashi Katsuhiko K   Ohta Hiroshi H   Yabuta Yukihiro Y   Kurimoto Kazuki K   Nakato Ryuichiro R   Yamada Yasuhiro Y   Shirahige Katsuhiko K   Saitou Mitinori M  

Cell stem cell 20130117 3

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  ...[more]

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