PMID- 24929238
OWN - NLM
STAT- MEDLINE
DCOM- 20140919
LR  - 20220408
IS  - 1095-564X (Electronic)
IS  - 0012-1606 (Linking)
VI  - 392
IP  - 2
DP  - 2014 Aug 15
TI  - Nanog co-regulated by Nodal/Smad2 and Oct4 is required for pluripotency in 
      developing mouse epiblast.
PG  - 182-92
LID - S0012-1606(14)00298-X [pii]
LID - 10.1016/j.ydbio.2014.06.002 [doi]
AB  - Nanog, a core pluripotency factor, is required for stabilizing pluripotency of 
      inner cell mass (ICM) and embryonic stem cells (ESCs), and survival of primordial 
      germ cells in mice. Here, we have addressed function and regulation of Nanog in 
      epiblasts of postimplantation mouse embryos by conditional knockdown (KD), 
      chromatin immunoprecipitation (ChIP) using in vivo epiblasts, and protein 
      interaction with the Nanog promoter in vitro. Differentiation of Nanog-KD 
      epiblasts demonstrated requirement for Nanog in stabilization of pluripotency. 
      Nanog expression in epiblast is directly regulated by Nodal/Smad2 pathway in a 
      visceral endoderm-dependent manner. Notably, Nanog promoters switch from 
      Oct4/Esrrb in ICM/ESCs to Oct4/Smad2 in epiblasts. Smad2 directly associates with 
      Oct4 to form Nanog promoting protein complex. Collectively, these data 
      demonstrate that Nanog plays a key role in stabilizing Epiblast pluripotency 
      mediated by Nodal/Smad2 signaling, which is involved in Nanog promoter switching 
      in early developing embryos.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Sun, Liang Tso
AU  - Sun LT
AD  - Department of Stem Cell Engineering, Institute for Frontier Medical Sciences, 
      Kyoto University, Kyoto 606-8507, Japan.
FAU - Yamaguchi, Shinpei
AU  - Yamaguchi S
AD  - Department of Stem Cell Engineering, Institute for Frontier Medical Sciences, 
      Kyoto University, Kyoto 606-8507, Japan.
FAU - Hirano, Kunio
AU  - Hirano K
AD  - Department of Stem Cell Engineering, Institute for Frontier Medical Sciences, 
      Kyoto University, Kyoto 606-8507, Japan.
FAU - Ichisaka, Tomoko
AU  - Ichisaka T
AD  - Department of Reprogramming Science, Center for iPS Cell Research and 
      Application, Kyoto University, Kyoto, 606-8507, Japan.
FAU - Kuroda, Takao
AU  - Kuroda T
AD  - Laboratory of Neural Differentiation, Graduate School of Brain Science, Doshisha 
      University, Kyoto 619-0225, Japan.
FAU - Tada, Takashi
AU  - Tada T
AD  - Department of Stem Cell Engineering, Institute for Frontier Medical Sciences, 
      Kyoto University, Kyoto 606-8507, Japan. Electronic address: 
      ttada@frontier.kyoto-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140612
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Nanog Homeobox Protein)
RN  - 0 (Nanog protein, mouse)
RN  - 0 (Nodal Protein)
RN  - 0 (Nodal protein, mouse)
RN  - 0 (Octamer Transcription Factor-3)
RN  - 0 (Pou5f1 protein, mouse)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad2 protein, mouse)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chromatin Immunoprecipitation
MH  - Gene Knockdown Techniques
MH  - Germ Layers/*embryology/metabolism
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Immunohistochemistry
MH  - Luciferases
MH  - Mice
MH  - *Models, Biological
MH  - Nanog Homeobox Protein
MH  - Nodal Protein/metabolism
MH  - Octamer Transcription Factor-3/genetics/metabolism
MH  - Pluripotent Stem Cells/metabolism/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Smad2 Protein/genetics/metabolism
OTO - NOTNLM
OT  - Epiblast
OT  - Nanog
OT  - Nodal
OT  - Oct4
OT  - Pluripotency
OT  - Smad2
EDAT- 2014/06/15 06:00
MHDA- 2014/09/23 06:00
CRDT- 2014/06/15 06:00
PHST- 2014/02/06 00:00 [received]
PHST- 2014/05/30 00:00 [revised]
PHST- 2014/06/03 00:00 [accepted]
PHST- 2014/06/15 06:00 [entrez]
PHST- 2014/06/15 06:00 [pubmed]
PHST- 2014/09/23 06:00 [medline]
AID - S0012-1606(14)00298-X [pii]
AID - 10.1016/j.ydbio.2014.06.002 [doi]
PST - ppublish
SO  - Dev Biol. 2014 Aug 15;392(2):182-92. doi: 10.1016/j.ydbio.2014.06.002. Epub 2014 
      Jun 12.