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| Status |
Public on Nov 11, 2011 |
| Title |
Activin/Nodal signalling controls divergent transcriptional networks in pluripotent and endoderm progenitors. |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Activin/Nodal signalling is necessary to maintain pluripotency of human Embryonic Stem Cells (hESCs) and to induce their differentiation towards endoderm. However, the mechanisms by which Activin/Nodal signalling achieves these opposite functions remain unclear. To unravel these mechanisms, we examined the transcriptional network controlled in hESCs by Smad2 and Smad3 which represent the direct effectors of Activin/Nodal signalling. These analyses reveal that Smad2/3 participate in the control of the core transcriptional network characterising pluripotency which includes Oct-4, Nanog, FoxD3, Dppa4, Tert, Myc and UTF-1. In addition, similar experiments performed on endoderm cells confirm that a broad part of the transcriptional network directing differentiation is downstream of Smad2/3. Therefore, Activin/Nodal signalling appears to control divergent transcriptional networks in hESCs and in endoderm. Importantly, we observed an overlap between the transcriptional network downstream of Nanog and Smad2/3 in hESCs while functional studies showed that both factors cooperate to control the expression of pluripotency genes. Therefore, the effect of Activin/Nodal signalling on pluripotency and differentiation could be dictated by tissue specific Smad2/3 partners such as Nanog, explaining the mechanisms by which signalling pathways can orchestrate divergent cell fate decisions.
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| Overall design |
Identification of Smad2/3 binding sites in pluripotent hESCs. 5 ChIP-Seq samples including 1 input control sample and 4 ChIP samples (two conditions x two replicates).
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| Contributor(s) |
Vallier L, Brown S, Trotter M |
| Citation(s) |
21630377 |
| Submission date |
Dec 14, 2009 |
| Last update date |
May 15, 2019 |
| Contact name |
Matthew Trotter |
| E-mail(s) |
mwbt2@cam.ac.uk
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| Organization name |
University of Cambridge
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| Department |
Department of Surgery
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| Lab |
Laboratory for Regenerative Medicine
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| Street address |
West Forvie Building, Forvie Site, Robinson Way
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0SZ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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| Samples (5)
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| Relations |
| SRA |
SRP002216 |
| BioProject |
PRJNA120331 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE19461_RAW.tar |
3.7 Gb |
(http)(custom) |
TAR (of BED, TXT) |
| GSE19461_README.txt |
1.6 Kb |
(ftp)(http) |
TXT |
| GSE19461_SMAD_XL_D0_BothReps_2M_RM.bed.gz |
140.6 Mb |
(ftp)(http) |
BED |
| GSE19461_SMAD_XL_D0_BoundRegions.gff.gz |
119.4 Kb |
(ftp)(http) |
GFF |
| GSE19461_SMAD_XL_D3_BothReps_2M_RM.bed.gz |
150.6 Mb |
(ftp)(http) |
BED |
| GSE19461_SMAD_XL_D3_BoundRegions.gff.gz |
130.7 Kb |
(ftp)(http) |
GFF |
SRA Run Selector |
| Processed data provided as supplementary file |
| Raw data are available in SRA |
| Processed data are available on Series record |
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