|
Status |
Public on Sep 01, 2021 |
Title |
De novo DNA methylation suppresses aberrant fate trajectory during epiblast transition [RNA-seq] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
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.
|
|
|
Overall design |
RNA were collected from undifferentiated ES cells and formative EpiLCs from Dnmt3a/3b double knockout cells with control
|
|
|
Contributor(s) |
Kinoshita M, Li MA, Barber M, Dietmann S, Smith A |
Citation(s) |
34518230 |
|
Submission date |
Sep 21, 2020 |
Last update date |
Nov 03, 2021 |
Contact name |
Irina Mohorianu |
E-mail(s) |
data-submissions@stemcells.cam.ac.uk
|
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 (4)
|
|
This SubSeries is part of SuperSeries: |
GSE158347 |
Disabling de novo DNA methylation in embryonic stem cells allows an illegitimate fate trajectory |
|
Relations |
BioProject |
PRJNA664787 |
SRA |
SRP284289 |