RNA- and ATAC-seq data from hESCs differentiated with Wnt and Activin with or without CPI-203
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA735402 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14740635.fastq.gz | Fastqsanger.gz | |||
| SRR14740636.fastq.gz | Fastqsanger.gz | |||
| SRR14740637.fastq.gz | Fastqsanger.gz | |||
| SRR14740638.fastq.gz | Fastqsanger.gz | |||
| SRR14740639.fastq.gz | Fastqsanger.gz |
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Project description:We report genome-wide changes in chromatin state and transcriptional output following Wnt-priming and subsequent Activin induced differentiation of human embryonic stem cell and the effects of BET bromodomain inhibition during Wnt-priming. The two signals, Wnt and Activin, although provided sequentially, result in stable mesendoderm differentiation (Yoney et al., 2018).
2021-06-06 | GSE176222 | GEO
Project description:Activin and Wnt signaling are necessary and sufficient for mesendoderm (ME) differentiation of human embryonic stem cells (hESCs). In this study, we report that during the Activin and Wnt induced ME differentiation, Activin/Smad2 induces decrease of the repressive histone modification H3K27me3 by promoting proteasome-dependent degradation of EZH2. As a result, recruitment of the forkhead protein FOXH1 on open chromatin regions integrates the signals of Activin/Smad2 and Wnt/β-catenin to activate the expression of the ME genes including HAS2 and ALDH3A2. Knockdown of HAS2 and ALDH3A2 greatly attenuates ME differentiation. These findings unveil a pathway from extracellular signals to epigenetic modification-mediated gene activation during ME commitment.
2018-09-29 | GSE113047 | GEO
Project description:It has now become clear that the process of fate specification during early embryogenesis is mediated by a handful of key signaling pathways. However, how the temporal and spatial integration of these signals plays out to give rise to self-organization of tissues remains obscure. Here we use artificial human gastruloids and quantitative single-cell analysis to dissect the temporal integration of two key pathways WNT and ACTIVIN that along with BMP control gastrulation and primitive streak patterning in model systems. We showed that ACTIVIN elicits a transient signaling response, as well as a transient induction of differentiation. However, unlike BMP and WNT, ACTIVIN cannot induce stable primitive streak formation and mesodermal patterning. Pre-exposure to WNT switches the response of cells to ACTIVIN whereby it becomes a concentration dependent morphogen. This provides evidence for WNT signaling memory that occurs at the transcriptional level and not as a modifier of ACTIVIN signaling dynamics.
2018-10-22 | GSE111717 | GEO
Project description:Human embryonic stem cells (hESCs) hold great value for future clinical applications. However, standard culture conditions maintain hESCs in a primed state, which bears heterogeneity and a tendency for spontaneous differentiation. To counter these drawbacks, hESCs have been converted to a naive state, but this has in turn restricted the efficiency of existing directed differentiation protocols. We show that adaptation of hESCs to Wnt-inhibiting condition (Wnt-i) conferred a unique transcriptional signature with high levels of pluripotency markers and reduced levels of differentiation markers. Moreover, neuronal and cardiac differentiation of Wnt-i hESCs progressed similarly to primed hESCs, unlike their naïve counterparts. Remarkably, in contrast to mouse, Wnt-i conditions failed to support direct derivation of hESCs, suggesting that active Wnt signaling is required for the transition from inner cell mass to hESCs. Wnt-i hESCs retained advantages of both primed and naive counterparts and may therefore be a better starting point for differentiation towards clinically desired cell types.
2020-10-13 | GSE105164 | GEO
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:Activin signalling controls the pluripotency of human embryonic stem cells (hESCs) by inducing the formation of nuclear Smad2/3-Nanog complexes that bind to and regulate several downstream targets. We aimed to clarify the transcriptional dynamics to the inhibition of Activin in hPSCs. To this end we performed microarray analysis of hPSCs treated with SB431542 (SB), an antagonist of the ALK4 and ALK7 type I Activin receptors, for early (2h, 4h and 8h) and late (24h and 48h) time points. Moreover, given our finding that Activin signalling regulates H3K4me3 of its target genes, we tested the transcriptional effect to the knock-down of the Mll/Set1 complex subunit Dpy30 by using shRNA. Finally, we also evaluated the transcriptional response to the knock-down of the Smad2/3 cofactor Nanog by using shRNA.
2015-01-01 | E-MTAB-2749 | biostudies-arrayexpress
Project description:Nodal/Activin signaling directs mesendoderm specification in early vertebrate embryogenesis. We have characterized transcriptional profiling of human embryonic stem cells and Activin-treated cells at different timepoints. In this dataset, we include the timecourse gene expression data obtained from hESC differentiation post Activin treatment, examining at day 0, 1, 3 and 5.
2011-05-21 | GSE29421 | GEO
Project description:Mesendoderm (ME) differentiation of human embryonic stem cells (hESCs) is directed by various extrinsic signals together with intrinsic epigenetic modifications. However, the dynamics of epigenetic modifications and their regulation to initiate ME differentiation remain elusive. In this study, we report that H3K27me3 is decreased during ME initiation, which is essential for the subsequent differentiation by collaborative effects of Activin and Wnt signaling. Mechanistically, Activin decreases the H3K27me3 level via disruption of the SUZ12-EZH2 interaction and EZH2 degradation mediated by Smad2. Our data suggest a two-step process of ME initiation: firstly H3K27me3-marked epigenetic priming and secondly transcription activation. Our findings unravel a critical role of H3K27me3 priming and a direct interaction between extrinsic signals and epigenetic modifications during ME initiation.
2016-11-30 | GSE81617 | GEO
Project description:In hESCs, Wnt3/β-catenin activity is low and Activin/SMAD signaling ensures NANOG expression to sustain pluripotency. In response to exogenous Wnt3 effectors, Activin/SMADs switch to cooperate with β-catenin and induce mesendodermal differentiation genes. We show here that the HIPPO effector YAP binds to the WNT3 gene enhancer and prevents the gene from being induced by Activin in proliferating hESCs. In the absence of YAP, Activin signaling is sufficient to induce expression of the endogenous Wnt3 cytokine, which stabilizes β-catenin and selectively activates genes required for cardiac mesoderm (ME) formation. Interestingly, Activin-stimulated YAP-knockout hESCs strongly express β-catenin-dependent cardiac mesoderm markers (BAF60c and HAND1), but unlike WT hESCs, fail to express cardiac inhibitor genes (CDX2, MSX1). Accordingly, YAP-/- cells treated with Activin alone can differentiate efficiently to beating cardiomyocytes in culture, bypassing the need for sequential treatment with exogenous Wnt ligand and Wnt inhibitors. Similarly, Activin in combination with small-molecule YAP inhibitors generates beating cardiomyocytes from wild-type hESCs following a one- step protocol. Our findings highlight an unanticipated role of YAP as an upstream regulator of WNT3 to maintain hESC pluripotency in the presence of Activin, and uncover a direct route for the development of human embryonic cardiac mesoderm.
2018-01-08 | GSE99202 | GEO