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| 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
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| 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.
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| Overall design |
Refer to individual Series
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| Citation(s) |
34518230 |
| |
| Submission date |
Sep 22, 2020 |
| Last update date |
Nov 03, 2021 |
| Contact name |
Irina Mohorianu |
| E-mail(s) |
data-submissions@stemcells.cam.ac.uk
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| Organization name |
University of Cambridge
|
| Department |
Wellcome-MRC Cambridge Stem Cell Institute
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| Street address |
Puddicombe Way
|
| City |
Cambridge |
| ZIP/Postal code |
CB2 0AW |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (18)
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| 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] |
|
| Relations |
| BioProject |
PRJNA664942 |
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