PMID- 25912690
OWN - NLM
STAT- MEDLINE
DCOM- 20150810
LR  - 20231115
IS  - 1095-564X (Electronic)
IS  - 0012-1606 (Print)
IS  - 0012-1606 (Linking)
VI  - 402
IP  - 2
DP  - 2015 Jun 15
TI  - Imprinted expression in cystic embryoid bodies shows an embryonic and not an 
      extra-embryonic pattern.
PG  - 291-305
LID - S0012-1606(15)00210-9 [pii]
LID - 10.1016/j.ydbio.2015.04.010 [doi]
AB  - A large subset of mammalian imprinted genes show extra-embryonic lineage (EXEL) 
      specific imprinted expression that is restricted to placental trophectoderm 
      lineages and to visceral yolk sac endoderm (ysE). Isolated ysE provides a 
      homogenous in vivo model of a mid-gestation extra-embryonic tissue to examine the 
      mechanism of EXEL-specific imprinted gene silencing, but an in vitro model of ysE 
      to facilitate more rapid and cost-effective experiments is not available. Reports 
      indicate that ES cells differentiated into cystic embryoid bodies (EBs) contain 
      ysE, so here we investigate if cystic EBs model ysE imprinted expression. The 
      imprinted expression pattern of cystic EBs is shown to resemble fetal liver and 
      not ysE. To investigate the reason for this we characterized the methylome and 
      transcriptome of cystic EBs in comparison to fetal liver and ysE, by whole genome 
      bisulphite sequencing and RNA-seq. Cystic EBs show a fetal liver pattern of 
      global hypermethylation and low expression of repeats, while ysE shows global 
      hypomethylation and high expression of IAPEz retroviral repeats, as reported for 
      placenta. Transcriptome analysis confirmed that cystic EBs are more similar to 
      fetal liver than ysE and express markers of early embryonic endoderm. Genome-wide 
      analysis shows that ysE shares epigenetic and repeat expression features with 
      placenta. Contrary to previous reports, we show that cystic EBs do not contain 
      ysE, but are more similar to the embryonic endoderm of fetal liver. This explains 
      why cystic EBs reproduce the imprinted expression seen in the embryo but not that 
      seen in the ysE.
CI  - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kulinski, Tomasz M
AU  - Kulinski TM
AD  - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 
      Lazarettgasse 14, AKH-BT25.3, 1090 Vienna, Austria. Electronic address: 
      tkulinski@ibb.waw.pl.
FAU - Casari, M Rita T
AU  - Casari MR
AD  - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 
      Lazarettgasse 14, AKH-BT25.3, 1090 Vienna, Austria. Electronic address: 
      rcasari@cemm.oeaw.ac.at.
FAU - Guenzl, Philipp M
AU  - Guenzl PM
AD  - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 
      Lazarettgasse 14, AKH-BT25.3, 1090 Vienna, Austria. Electronic address: 
      pguenzl@cemm.oeaw.ac.at.
FAU - Wenzel, Daniel
AU  - Wenzel D
AD  - IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 
      Dr. Bohr Gasse 3, 1030 Vienna, Austria. Electronic address: 
      daniel.wenzel@imba.oeaw.ac.at.
FAU - Andergassen, Daniel
AU  - Andergassen D
AD  - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 
      Lazarettgasse 14, AKH-BT25.3, 1090 Vienna, Austria. Electronic address: 
      dandergassen@cemm.oeaw.ac.at.
FAU - Hladik, Anastasiya
AU  - Hladik A
AD  - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 
      Lazarettgasse 14, AKH-BT25.3, 1090 Vienna, Austria; Department of Medicine 1, 
      Laboratory of Infection Biology, Medical University of Vienna, 1090 Vienna, 
      Austria. Electronic address: ahladik@cemm.oeaw.ac.at.
FAU - Datlinger, Paul
AU  - Datlinger P
AD  - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 
      Lazarettgasse 14, AKH-BT25.3, 1090 Vienna, Austria. Electronic address: 
      pdatlinger@cemm.oeaw.ac.at.
FAU - Farlik, Matthias
AU  - Farlik M
AD  - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 
      Lazarettgasse 14, AKH-BT25.3, 1090 Vienna, Austria. Electronic address: 
      mfarlik@cemm.oeaw.ac.at.
FAU - Theussl, H-Christian
AU  - Theussl HC
AD  - IMP/IMBA Transgenic Service, Institute of Molecular Pathology (IMP), Dr. Bohr 
      Gasse 7, 1030 Vienna, Austria. Electronic address: christian.theussl@imp.ac.at.
FAU - Penninger, Josef M
AU  - Penninger JM
AD  - IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 
      Dr. Bohr Gasse 3, 1030 Vienna, Austria. Electronic address: 
      josef.penninger@imba.oeaw.ac.at.
FAU - Knapp, Sylvia
AU  - Knapp S
AD  - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 
      Lazarettgasse 14, AKH-BT25.3, 1090 Vienna, Austria; Department of Medicine 1, 
      Laboratory of Infection Biology, Medical University of Vienna, 1090 Vienna, 
      Austria. Electronic address: sknapp@cemm.oeaw.ac.at.
FAU - Bock, Christoph
AU  - Bock C
AD  - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 
      Lazarettgasse 14, AKH-BT25.3, 1090 Vienna, Austria. Electronic address: 
      cbock@cemm.oeaw.ac.at.
FAU - Barlow, Denise P
AU  - Barlow DP
AD  - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 
      Lazarettgasse 14, AKH-BT25.3, 1090 Vienna, Austria. Electronic address: 
      dbarlow@cemm.oeaw.ac.at.
FAU - Hudson, Quanah J
AU  - Hudson QJ
AD  - CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 
      Lazarettgasse 14, AKH-BT25.3, 1090 Vienna, Austria. Electronic address: 
      qhudson@cemm.oeaw.ac.at.
LA  - eng
GR  - P 25185/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150424
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Differentiation/physiology
MH  - Chromatin Immunoprecipitation
MH  - Computational Biology
MH  - *DNA Methylation
MH  - Embryoid Bodies/*metabolism
MH  - Endoderm/metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Developmental/*genetics
MH  - Genomic Imprinting/*genetics
MH  - Histological Techniques
MH  - In Situ Hybridization
MH  - Mice
MH  - *Models, Biological
MH  - Molecular Sequence Data
MH  - Sequence Analysis, RNA
MH  - Yolk Sac/cytology/metabolism
PMC - PMC4454777
OTO - NOTNLM
OT  - Cystic embryoid bodies (EBs)
OT  - DNA methylation
OT  - Genomic imprinting
OT  - Visceral endoderm (VE)
OT  - Visceral yolk sac (VYS)
OT  - Visceral yolk sac Endoderm (ysE)
EDAT- 2015/04/29 06:00
MHDA- 2015/08/11 06:00
PMCR- 2015/06/15
CRDT- 2015/04/28 06:00
PHST- 2014/09/16 00:00 [received]
PHST- 2015/04/08 00:00 [revised]
PHST- 2015/04/16 00:00 [accepted]
PHST- 2015/04/28 06:00 [entrez]
PHST- 2015/04/29 06:00 [pubmed]
PHST- 2015/08/11 06:00 [medline]
PHST- 2015/06/15 00:00 [pmc-release]
AID - S0012-1606(15)00210-9 [pii]
AID - 10.1016/j.ydbio.2015.04.010 [doi]
PST - ppublish
SO  - Dev Biol. 2015 Jun 15;402(2):291-305. doi: 10.1016/j.ydbio.2015.04.010. Epub 2015 
      Apr 24.