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| Status |
Public on Jun 11, 2018 |
| Title |
Oct4 regulates the embryonic axis and coordinates exit from pluripotency and germ layer specification in the mouse embryo |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Lineage segregation in the mouse embryo is a finely controlled process dependent upon coordination of signalling pathways and transcriptional responses. We employed conditional deletion of Oct4 to investigate consequences of interference with embryonic patterning and lineage specification. Nanog becomes upregulated in the first epiblast cells to lose Oct4, leading to an expanded Nanog-positive domain. The primitive streak forms in the presumptive proximal posterior region, but epithelial to mesenchymal transition is impeded by dramatic increase of E-cadherin, leading to complete disorganisation and failure to generate germ layers. Formerly, expression domains of lineage markers were disrupted. Specifically, definitive endoderm expanded, the boundaries between presumptive anterior and posterior domains blurred and an ectopic posterior-like region appeared anteriorly, suggesting a role for Oct4 in maintaining the embryonic axis. Despite intermixing of lineage marker domains in mutants, cells co-expressing distinct lineage genes were not observed, suggesting that Oct4 deletion does not alter the connectivity of the transcription networks which underlie cell fate decisions in vivo. Molecular profiling corroborated genome-wide posteriorisation of mutants and disrupted expression of genes involved in gastrulation. Lastly, we confirmed a requirement for Oct4 in self-renewal of post-implantation epiblast ex vivo
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| Overall design |
mRNA profiling of OCT4- and OCT4+ mouse in post implantation stage
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| Contributor(s) |
Chia le Bin G, Mulas C, Jones KA, Stirparo GG, Nichols J |
| Citation(s) |
29915126 |
| Submission date |
Sep 01, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Giuliano Giuseppe Stirparo |
| E-mail(s) |
giulianostirparo@gmail.com
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| Organization name |
University of Cambridge
|
| Department |
Wellcome MRC Cambridge Stem Cell
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| Lab |
Jeffrey Cheah Biomedical Centre
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| Street address |
Puddicombe Way
|
| City |
Cambridge |
| State/province |
Cambridgeshire |
| ZIP/Postal code |
CB2 0AW |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA401721 |
| SRA |
SRP116950 |
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