PMID- 23799023
OWN - NLM
STAT- MEDLINE
DCOM- 20140305
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 6
DP  - 2013
TI  - The immunoglobulin superfamily protein differentiation of embryonic stem cells 1 
      (dies1) has a regulatory role in preadipocyte to adipocyte conversion.
PG  - e65531
LID - 10.1371/journal.pone.0065531 [doi]
LID - e65531
AB  - Differentiation of Embryonic Stem Cells 1 (Dies1) was recently identified as a 
      novel type I immunoglobulin (IgG) domain-containing plasma membrane protein 
      important for effective differentiation of a murine pluripotent embryonic stem 
      cell line. In this setting, Dies1 enhances bone morphogenetic protein 4 (BMP4) 
      signaling. Here we show Dies1 transcript expression is induced  approximately 225-fold during 
      in vitro adipogenesis of 3T3-L1 murine preadipocytes. Immunocytochemical imaging 
      using ectopic expression of Flag-tagged Dies1 in 3T3-L1 adipocytes revealed 
      localization to the adipocyte plasma membrane. Modulation of adipocyte phenotype 
      with with tumor necrosis factor-alpha (TNFalpha) treatment or by siRNA knockdown of the 
      master pro-adipogenic transcription factor peroxisome proliferator activated 
      receptor gamma (PPARgamma) resulted in a 90% and 60% reduction of Dies1 transcript 
      levels, respectively. Moreover, siRNA-mediated Dies1 knockdown in 3T3-L1 
      preadipocytes inhibited adipogenic conversion. Such cultures had a 35% decrease 
      in lipid content and a 45%-65% reduction in expression of key adipocyte 
      transcripts, including that for PPARgamma. The standard protocol for full in vitro 
      adipogenic conversion of committed preadipocytes, such as 3T3-L1, does not 
      include BMP4 treatment. Thus we posit the positive role of Dies1 in adipogenesis, 
      unlike that for Dies1 in differentiation of embryonic stem cells, does not 
      include its pro-BMP4 effects. In support of this idea, 3T3-L1 adipocytes knocked 
      down for Dies1 did not evidence decreased phospho-Smad1 levels upon BMP4 
      exposure. qPCR analysis of Dies1 transcript in multiple murine and human tissues 
      reveals high enrichment in white adipose tissue (WAT). Interestingly, we observed 
      a 10-fold induction of Dies1 transcript in WAT of fasted vs. fed mice, suggesting 
      a role for Dies1 in nutritional response of mature fat cells in vivo. Together 
      our data identify Dies1 as a new differentiation-dependent adipocyte plasma 
      membrane protein whose expression is required for effective adipogenesis and that 
      may also play a role in regard to nutritional status in WAT.
FAU - Ren, Gang
AU  - Ren G
AD  - Department of Biochemistry and Cancer Biology, University of Toledo College of 
      Medicine, Toledo, Ohio, USA.
FAU - Beech, Cameron
AU  - Beech C
FAU - Smas, Cynthia M
AU  - Smas CM
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130617
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Bmp4 protein, mouse)
RN  - 0 (Bone Morphogenetic Protein 4)
RN  - 0 (DNA Primers)
RN  - 0 (Immunoglobulins)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Vsir protein, mouse)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*cytology
MH  - Animals
MH  - Base Sequence
MH  - Bone Morphogenetic Protein 4/metabolism
MH  - Cell Differentiation/*physiology
MH  - Cell Line
MH  - DNA Primers
MH  - Embryonic Stem Cells/*metabolism
MH  - Gene Expression Profiling
MH  - Humans
MH  - Immunoglobulins/*physiology
MH  - Male
MH  - Membrane Proteins/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/genetics
MH  - RNA, Small Interfering
MH  - Signal Transduction
PMC - PMC3684596
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/06/27 06:00
MHDA- 2014/03/07 06:00
PMCR- 2013/06/17
CRDT- 2013/06/27 06:00
PHST- 2013/01/30 00:00 [received]
PHST- 2013/05/01 00:00 [accepted]
PHST- 2013/06/27 06:00 [entrez]
PHST- 2013/06/27 06:00 [pubmed]
PHST- 2014/03/07 06:00 [medline]
PHST- 2013/06/17 00:00 [pmc-release]
AID - PONE-D-13-06047 [pii]
AID - 10.1371/journal.pone.0065531 [doi]
PST - epublish
SO  - PLoS One. 2013 Jun 17;8(6):e65531. doi: 10.1371/journal.pone.0065531. Print 2013.