Genomics

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Activin/Nodal signalling controls divergent transcriptional networks in pluripotent and endoderm progenitors.


ABSTRACT: 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. 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).

ORGANISM(S): Homo sapiens  

SUBMITTER: Matthew Trotter  Ludovic Vallier   Stephanie Brown    

PROVIDER: E-GEOD-19461 | ArrayExpress | 2011-11-11

SECONDARY ACCESSION(S): SRP002216GSE19461PRJNA120331

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Activin/Nodal signaling controls divergent transcriptional networks in human embryonic stem cells and in endoderm progenitors.

Brown Stephanie S   Teo Adrian A   Pauklin Siim S   Hannan Nicholas N   Cho Candy H-H CH   Lim Bing B   Vardy Leah L   Dunn N Ray NR   Trotter Matthew M   Pedersen Roger R   Vallier Ludovic L  

Stem cells (Dayton, Ohio) 20110801 8


Activin/Nodal signaling is necessary to maintain pluripotency of human embryonic stem cells (hESCs) and to induce their differentiation toward endoderm. However, the mechanisms by which Activin/Nodal signaling 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 signaling. These analyses reveal that Smad2/3 participate in the control of t  ...[more]

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