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Title: Effect of Tet1-knockdown on gene expression in mouse ES cells cultured in ES and TS cell culture conditions      
dateReleased:
02-07-2011
description:
TET-family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem (ES) cells. ES cells depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1, and display hyperactive Nodal signalling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in vitro. In Fgf4- and heparin-supplemented culture conditions that favor derivation of trophoblast stem (TS) cells, Tet1-depleted ES cells activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in mid-gestation embryo chimeras. Consistent with these findings, Tet1-depleted ES cells form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm and ectopic appearance of trophoblastic giant cells. Thus Tet1 functions to regulate the lineage differentiation potential of ES cells. Here, we performed whole-genome transcriptome profiling of ES cells stably depleted of Tet1 by shRNA knockdown (Tet1-kd) cultured in either standard ES cell or in TS cell culture conditions. Gene expression changes in Tet1-kd ES cells were fairly modest compared to control (GFP-kd) cells, although gene ontology (GO) analysis of differentially expressed genes yielded many terms related to embryonic development and cell cycle regulation. In TS cell culture conditions, a core set of genes defining trophectodermal cell differentiation, including Cdx2, Eomes and Tead4, was enriched in Tet1-kd compared to GFP-kd cells. A total of 27 samples were analysed with at least 3 replicates in each group. Control/reference samples comprise ES cells cultured in standard ES cell media (true ES cells) and TS cells cultured in Fgf4/heparin-supplemented (TS) media (true TS cells). We compared Tet1-kd ES cells with GFP-kd ES cells cultured in either ES or TS cell media. In addition, we included a set of Tet1-kd subclones (Tet1-kd-sc) cultured in TS cell condition and a set of untransfected ES cells (parental control) cultured in TS cell condition.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-26900
refinement:
raw
alternateIdentifiers:
26900
keywords:
functional genomics
dateModified:
03-27-2012
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-MEXP-1175
name:
Illumina MouseWG-6 v2.0 Expression BeadChip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-26900/E-GEOD-26900.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-26900/E-GEOD-26900.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26900
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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