Investigating the role of NODAL signalling in preimplantation human embryos
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE244736 | GEO | 2024/11/03
REPOSITORIES: GEO
Similar Datasets
Project description:Investigating the role of NODAL signalling in preimplantation human embryos
| PRJNA1024471 | ENA
Project description: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).
2011-11-11 | E-GEOD-19461 | biostudies-arrayexpress
Project description: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.
2011-11-11 | GSE19461 | GEO
Project description:This experiment was designed to monitor the gene expression changes induced by the knockdown of WTAP in human pluripotent stem cells (hPSCs) during the exit from pluripotency induced by the inhibition of Activin/Nodal signalling. hPSCs carrying a tetracycline-inducible short hairpin RNA (shRNA) against WTAP were cultured in control conditions or in presence of tetracycline (TET) to drive gene knockdown. Cells were monitored by RNA-seq in the pluripotent state (culture conditions containing Activin), or at various time points after inhibition of Activin/Nodal signalling with the receptor antagonist SB-431542 (SB). Samples were collected after 2h, 8h and 32h.
2018-01-04 | E-MTAB-5230 | biostudies-arrayexpress
Project description:We have been able to derive EpiSC-like pESC lines from in vivo produced porcine blastocysts. Our cell lines showed AP activity, expressions of the genes Oct4, Sox2, Nanog, Rex1, TDGF1, bFGF, FGFR1, FGFR2, Nodal and Activin-A involved in pluripotency and signaling pathways and in vitro differentiation potential, displaying similarities to epiblast stem cells or hES cells.
2011-12-31 | GSE32506 | GEO
Project description:Although much is known about the pluripotency self-renewal circuitry, the molecular events that lead embryonic stem cells (ESCs) exit from pluripotency and begin differentiation are largely unknown. We found that the zinc finger transcription factor Snai1, involved in gastrulation and epithelial- mesenchymal transition (EMT) is already expressed in the inner cell mass of the preimplantation blastocysts. In ESCs Snai1 does not respond to TGFα or BMP4 signalling but it is induced by retinoic acid (RA) treatment, which induces the binding, on the Snai1 promoter, of the retinoid receptors RARγ and RXRα the dissociation of the Polycomb repressor compex 2 (PRC2) which results in the decrease of H3K27me3 and the increase of histone H3K4me3. Snai1 mediates the repression of pluripotency genes by binding directly to the promoters of Nanog, Nr5a2, Tcl1, c-Kit, and Tcfcp2l1. The transient activation of Snai1 in embryoid bodies induces the expression of the markers of all three germ layers. These results suggest that Snai1 is a key factor that triggers ESCs exit from the pluripotency state and initiate their differentiation processes. microarray analysis of embryonic stem cells (ESC) expressing Snail-ER at various time points of induction with 4-OHT
2015-01-12 | E-GEOD-57854 | biostudies-arrayexpress
Project description:Although much is known about the pluripotency self-renewal circuitry, the molecular events that lead embryonic stem cells (ESCs) exit from pluripotency and begin differentiation are largely unknown. We found that the zinc finger transcription factor Snai1, involved in gastrulation and epithelial- mesenchymal transition (EMT) is already expressed in the inner cell mass of the preimplantation blastocysts. In ESCs Snai1 does not respond to TGFα or BMP4 signalling but it is induced by retinoic acid (RA) treatment, which induces the binding, on the Snai1 promoter, of the retinoid receptors RARγ and RXRα the dissociation of the Polycomb repressor compex 2 (PRC2) which results in the decrease of H3K27me3 and the increase of histone H3K4me3. Snai1 mediates the repression of pluripotency genes by binding directly to the promoters of Nanog, Nr5a2, Tcl1, c-Kit, and Tcfcp2l1. The transient activation of Snai1 in embryoid bodies induces the expression of the markers of all three germ layers. These results suggest that Snai1 is a key factor that triggers ESCs exit from the pluripotency state and initiate their differentiation processes.
2015-01-12 | GSE57854 | GEO
Project description:This experiment was designed to probe the function of Activin/Nodal signalling in the deposition of m6A in human pluripotent stem cells (hPSCs). hPSCs were cultured in presence of Activin or subjected to short-term inhibition of Activin/Nodal signalling for 2h using the receptor antagonist SB-431542 (IP). The global abundance of m6A was then measured by nuclear-enriched methylated RNA immunoprecipitation followed by deep sequencing (NeMeRIP-seq). Pre-NeMeRIP input RNA was used as control to normalise for the changes in gene expression in the two conditions.
2017-12-26 | E-MTAB-5229 | biostudies-arrayexpress
Project description:A comprehensive search for downstream genes is necessary for understanding of functions of Nodal signaling in embryos of the ascidian Ciona intestinalis. The level of mRNA expression in Nodal-overexpressing embryos was compared with that in normal embryos at the late gastrula stage by a microarray analysis. Overexpression of Ci-nodal elevated the level of expression of 115 genes more than two-fold. These candidate target genes include those encoding transcription factors, proteins involved in cell-cell communication, and extracellular matrix components. Many of these genes were expressed in the neural plate at the late gastrula stage. Overexpression of nodal also affected the expression of genes involved in the planar cell polarity pathway and Wnt/Ca2+ pathway (prickle, Rho-like2, and PLC2), and delta1-protocadherin-like. Keywords: ascidian, Ciona intestinalis, Nodal, embryogenesis, gene expression profile
2010-01-26 | GSE14567 | GEO
Project description:Our understanding of signalling pathways that regulate human pluripotent epiblast cells is limited, despite their fundamental biological and clinical importance. In this study, we mined human embryo transcriptomics datasets, and identified expression of transcripts for the insulin and insulin growth factor 1 (IGF1) receptors, along with IGF1 ligand. Human embryos cultured in medium supplemented with IGF1 showed an increase in the proportion of NANOG-expressing pluripotent epiblast progenitor cells. Consequently, we generated a minimal chemically-defined culture medium informed by the signalling environment of the human embryo. We derived several human embryonic stem cell (hESC) lines and reprogrammed fibroblasts to induced pluripotent stem cells (iPSCs) in these conditions. Transcriptome and protein expression analyses confirmed that these hESCs and iPSCs expressed pluripotency-associated genes. Moreover, hESCs and iPSCs retained high viability, the ability to undergo spontaneous and directed differentiation, and a normal karyotype. By contrast, fibroblast growth factor 2 (FGF2) was detrimental to epiblast development and dispensable for hESC cultures maintained in exogenous insulin or IGF1. This is the first example of how integrating signalling insights from human blastocysts can be used to define hESC culture conditions that more closely recapitulate the embryonic niche.
2020-01-03 | GSE126488 | GEO