Disabling de novo DNA methylation in embryonic stem cells allows an illegitimate fate trajectory
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA664942 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12683317.fastq.gz | Fastqsanger.gz | |||
| SRR12683318.fastq.gz | Fastqsanger.gz | |||
| SRR12683319.fastq.gz | Fastqsanger.gz | |||
| SRR12683320.fastq.gz | Fastqsanger.gz | |||
| SRR12683321.fastq.gz | Fastqsanger.gz |
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Project description: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.
2021-08-31 | GSE158347 | GEO
Project description:Genome remethylation is essential for mammalian development. Here we examined cell fate in the absence of de novo DNA methyltransferases. We found that embryonic stem (ES) cells deficient for Dnmt3a and Dnmt3b are rapidly eliminated from chimaeras. Pluripotency progression is derailed towards extra-embryonic trophoblast. This aberrant trajectory is propelled by failure to methylate and suppress expression of Ascl2 during formative transition. Ascl2 deletion rescues transition and improves contribution to chimaeric epiblast but mutant cells are progressively lost in later development. These findings indicate that methylation constrains transcriptome trajectories during developmental transitions by silencing potentially disruptive genes. This submission is RNA-seq.
2021-09-01 | GSE158310 | GEO
Project description:Genome remethylation is essential for mammalian development. Here we examined cell fate in the absence of de novo DNA methyltransferases. We found that embryonic stem (ES) cells deficient for Dnmt3a and Dnmt3b are rapidly eliminated from chimaeras. Pluripotency progression is derailed towards extra-embryonic trophoblast. This aberrant trajectory is propelled by failure to methylate and suppress expression of Ascl2 during formative transition. Ascl2 deletion rescues transition and improves contribution to chimaeric epiblast but mutant cells are progressively lost in later development. These findings indicate that methylation constrains transcriptome trajectories during developmental transitions by silencing potentially disruptive genes. This submission is ATAC-seq.
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Project description:DNA-PKcs Suppresses Illegitimate Chromosome Rearrangements
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Project description:De novo DNA methylation suppresses aberrant fate trajectory during epiblast transition [RNA-seq]
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