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Series GSE158347 Query DataSets for GSE158347
Status Public on Aug 31, 2021
Title Disabling de novo DNA methylation in embryonic stem cells allows an illegitimate fate trajectory
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Genome remethylation is essential for mammalian development but specific reasons are unclear. Here we examined embryonic stem (ES) cell fate in the absence of de novo DNA methyltransferases. We observed that ES cells deficient for both Dnmt3a and Dnmt3b are rapidly eliminated from chimeras. On further investigation we found that in vivo and in vitro the formative pluripotency transition is derailed toward production of trophoblast. This aberrant trajectory is associated with failure to suppress activation of Ascl2. Ascl2 encodes a bHLH transcription factor expressed in the placenta. Misexpression of Ascl2 in ES cells provokes transdifferentiation to trophoblast-like cells. Conversely, Ascl2 deletion rescues formative transition of Dnmt3a/b mutants and improves contribution to chimeric epiblast. Thus, de novo DNA methylation safeguards against ectopic activation of Ascl2. However, Dnmt3a/b-deficient cells remain defective in ongoing embryogenesis. We surmise that multiple developmental transitions may be secured by DNA methylation silencing potentially disruptive genes.

This SuperSeries is composed of the SubSeries listed below.
Overall design Refer to individual Series
Citation(s) 34518230
Submission date Sep 22, 2020
Last update date Nov 03, 2021
Contact name Irina Mohorianu
Organization name University of Cambridge
Department Wellcome-MRC Cambridge Stem Cell Institute
Street address Puddicombe Way
City Cambridge
ZIP/Postal code CB2 0AW
Country United Kingdom
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (18)
GSM4797285 WT.AFKD2
GSM4797286 KO.AFKD2
GSM4797287 WT.2iL
This SuperSeries is composed of the following SubSeries:
GSE158310 De novo DNA methylation suppresses aberrant fate trajectory during epiblast transition [RNA-seq]
GSE158344 ­De novo DNA methylation suppresses aberrant fate trajectory during epiblast transition [ATAC-seq]
BioProject PRJNA664942

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE158347_RAW.tar 2.0 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp

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