PMID- 21341991
OWN - NLM
STAT- MEDLINE
DCOM- 20120216
LR  - 20211020
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Print)
IS  - 1547-3287 (Linking)
VI  - 20
IP  - 11
DP  - 2011 Nov
TI  - L3MBTL1 deficiency directs the differentiation of human embryonic stem cells 
      toward trophectoderm.
PG  - 1889-900
LID - 10.1089/scd.2010.0437 [doi]
AB  - Human embryonic stem cells (hESCs) can be used to study the early events in human 
      development and, hopefully, to understand how to differentiate human pluripotent 
      cells for clinical use. To define how L3MBTL1, a chromatin-associated polycomb 
      group protein with transcriptional repressive activities, regulates early events 
      in embryonic cell differentiation, we created hESC lines that constitutively 
      express shRNAs directed against L3MBTL1. The L3MBTL1 knockdown (KD) hESCs 
      maintained normal morphology, proliferation, cell cycle kinetics, cell surface 
      markers, and karyotype after 40 passages. However, under conditions that promote 
      spontaneous differentiation, the L3MBTL1 KD cells differentiated into a 
      relatively homogeneous population of large, flat trophoblast-like cells, unlike 
      the multilineage differentiation seen with the control cells. The differentiated 
      L3MBTL1 KD cells expressed numerous trophoblast markers and secreted placental 
      hormones. Although the L3MBTL1 KD cells could be induced to differentiate into 
      various embryonic lineages, they adopted an exclusive trophoblast fate during 
      spontaneous differentiation. Our data demonstrate that depletion of L3MBTL1 does 
      not affect hESC self-renewal, rather it enhances differentiation toward 
      extra-embryonic trophoblast tissues.
FAU - Hoya-Arias, Ruben
AU  - Hoya-Arias R
AD  - Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial 
      Sloan-Kettering Cancer Center, New York, New York 10065, USA.
FAU - Tomishima, Mark
AU  - Tomishima M
FAU - Perna, Fabiana
AU  - Perna F
FAU - Voza, Francesca
AU  - Voza F
FAU - Nimer, Stephen D
AU  - Nimer SD
LA  - eng
GR  - R01 CA102202/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110403
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (Antigens, Differentiation)
RN  - 0 (BMP4 protein, human)
RN  - 0 (Bone Morphogenetic Protein 4)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (L3MBTL1 protein, human)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Antigens, Differentiation/genetics/metabolism
MH  - Bone Morphogenetic Protein 4/pharmacology/physiology
MH  - *Cell Differentiation/drug effects
MH  - Cell Line
MH  - Cell Proliferation
MH  - Cell Shape
MH  - Chromosomal Proteins, Non-Histone/*deficiency/genetics
MH  - Coculture Techniques
MH  - Ectoderm/*cytology
MH  - Embryonic Stem Cells/*physiology
MH  - Gene Expression
MH  - Gene Knockdown Techniques
MH  - Green Fluorescent Proteins/metabolism
MH  - Humans
MH  - Microscopy, Fluorescence
MH  - RNA Interference
MH  - Recombinant Proteins/metabolism
MH  - Repressor Proteins
MH  - Trophoblasts/*cytology
MH  - Tumor Suppressor Proteins
PMC - PMC3202892
EDAT- 2011/02/24 06:00
MHDA- 2012/02/18 06:00
PMCR- 2012/11/01
CRDT- 2011/02/24 06:00
PHST- 2011/02/24 06:00 [entrez]
PHST- 2011/02/24 06:00 [pubmed]
PHST- 2012/02/18 06:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - 10.1089/scd.2010.0437 [pii]
AID - 10.1089/scd.2010.0437 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2011 Nov;20(11):1889-900. doi: 10.1089/scd.2010.0437. Epub 2011 
      Apr 3.