PMID- 21948699
OWN - NLM
STAT- MEDLINE
DCOM- 20120312
LR  - 20211020
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 29
IP  - 12
DP  - 2011 Dec
TI  - Phosphatase and tensin homolog regulates the pluripotent state and lineage fate 
      choice in human embryonic stem cells.
PG  - 1952-62
LID - 10.1002/stem.748 [doi]
AB  - Understanding the intrinsic and extrinsic signals that regulate the molecular 
      basis of the pluripotent state may improve our understanding of mammalian 
      embryogenesis, different states of pluripotency, and our ability to tailor 
      lineage differentiation. Although the role of the PI3K/Akt pathway in the 
      self-renewal and maintenance of mESCs is well-established, the specific 
      contribution of the pathway or of its negative regulator, PTEN, in the 
      maintenance of the human pluripotent state is less understood. To explore the 
      PI3K/AKT pathway in human embryonic stem cell (hESC) pluripotency and 
      differentiation, we generated stable PTEN knockdown (KD) hESCs using short 
      hairpin RNA. Similar to mESCs, we found that PTEN KD hESCs have increased 
      self-renewal, cell survival, and proliferation over multiple passages compared to 
      control cells. However, in contrast to mESCs, in vitro, PTEN KD hESCs 
      differentiated inefficiently in directed differentiation assays, in part due to 
      the continued maintenance of OCT4 and NANOG expression. In teratoma assays, PTEN 
      KD hESCs generated tissues from the three germ layers, although with a bias 
      toward neuroectoderm differentiation. These results demonstrate that PTEN is a 
      key regulator of hESC growth and differentiation, and manipulation of this 
      pathway may improve our ability to regulate and understand the pluripotent state.
CI  - Copyright (c) 2011 AlphaMed Press.
FAU - Alva, Jackelyn A
AU  - Alva JA
AD  - Department of Microbiology, Immunology, and Molecular Genetics, University of 
      California, Los Angeles, California 90095, USA.
FAU - Lee, Grace E
AU  - Lee GE
FAU - Escobar, Erika E
AU  - Escobar EE
FAU - Pyle, April D
AU  - Pyle AD
LA  - eng
GR  - T32 CA009120/CA/NCI NIH HHS/United States
GR  - T32CA009120-33/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Homeodomain Proteins)
RN  - 0 (NANOG protein, human)
RN  - 0 (Nanog Homeobox Protein)
RN  - 0 (Octamer Transcription Factor-3)
RN  - 0 (POU5F1 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Animals
MH  - *Cell Differentiation
MH  - Cell Line
MH  - Cell Lineage
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Embryonic Stem Cells/*cytology/metabolism
MH  - Gene Knockdown Techniques
MH  - Homeodomain Proteins/genetics/metabolism
MH  - Humans
MH  - Lentivirus/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Nanog Homeobox Protein
MH  - Octamer Transcription Factor-3/genetics/metabolism
MH  - PTEN Phosphohydrolase/genetics/*metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Pluripotent Stem Cells/*cytology/metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Signal Transduction
MH  - Teratoma/genetics/metabolism/pathology
PMC - PMC3898662
MID - NIHMS488821
COIS- Disclosure of Potential Conflicts of Interest The authors indicate no potential 
      conflicts of interest.
EDAT- 2011/09/29 06:00
MHDA- 2012/03/13 06:00
PMCR- 2014/01/22
CRDT- 2011/09/28 06:00
PHST- 2011/09/28 06:00 [entrez]
PHST- 2011/09/29 06:00 [pubmed]
PHST- 2012/03/13 06:00 [medline]
PHST- 2014/01/22 00:00 [pmc-release]
AID - 10.1002/stem.748 [doi]
PST - ppublish
SO  - Stem Cells. 2011 Dec;29(12):1952-62. doi: 10.1002/stem.748.