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| Status |
Public on Jan 31, 2011 |
| Title |
Graded Nodal/Activin Signaling Governs ES Cell Fate Decisions via Differential Recruitment of Phospho-Smad2 to Oct4 and Distinct Target Gene Subsets. |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The Nodal/Activin morphogens are secreted signaling molecules that form concentration gradients during early embryogenesis providing stem cells with positional information and differentiation instructions important for embryonic patterning. The molecular basis driving stem cell interpretation of signaling gradients and the undertaking of distinct cell fate decisions remains poorly understood. We show that perturbation of endogenous Nodal/Activin signaling in ES cells leads to exit from self renewal towards mesendodermal differentiation at high signaling and trophectoderm induction during low signaling. ChIP-seq of Phospho-Smad2, the downstream transcription factor of the Nodal/Activin pathway reveals binding to distinct subsets of target genes in a dose dependent manner including the promoter region of the Oct4 master regulator of stemness. Consequently, both Oct4 mRNA and protein levels are directly driven by graded Nodal/Activin signaling. Hence stem cells interpret and carry out differential Nodal/Activin signaling instructions via a corresponding gradient of Smad2 phosphorylation that selectively titers self renewal against alternative differentiation programs.
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| Overall design |
3 pSmad2 ChIP samples corresponding to ES cells pretreated for 6 hours in 10uM SB followed by 18 hours in 25ng/ml Activin, 1/5000 DMSO and 10uM SB in 20% KSR media. Controls include the corresponding input DNA for each treatment.
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| Contributor(s) |
Lee KL, Orlov YL, Lim B |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Aug 12, 2010 |
| Last update date |
May 15, 2019 |
| Contact name |
Yuriy L Orlov |
| E-mail(s) |
orlovy@gis.a-star.edu.sg
|
| Organization name |
Genome Institute of Singapore
|
| Department |
Computational Systems Biology
|
| Street address |
60 Biopolis Street
|
| City |
Singapore |
| ZIP/Postal code |
138672 |
| Country |
Singapore |
| |
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| Platforms (1) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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| Samples (6)
|
| GSM578474 |
pSmad2 ChIPSeq of ES cells treated for 18 hours in 25ng/ml Activin |
| GSM578475 |
pSmad2 ChIPSeq of ES cells treated for 18 hours in 1/5000 DMSO |
| GSM578476 |
pSmad2 ChIPSeq of ES cells treated for 18 hours in 10uM SB |
| GSM578477 |
pSmad2 input DNA Seq of ES cells treated for 18 hours in 25ng/ml Activin |
| GSM578478 |
pSmad2 input DNA Seq of ES cells treated for 18 hours in 1/5000 DMSO |
| GSM578479 |
pSmad2 input DNA Seq of ES cells treated for 18 hours in 10uM SB |
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| Relations |
| SRA |
SRP003467 |
| BioProject |
PRJNA131845 |
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