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Endogenous suppression of WNT signalling in human embryonic stem cells leads to low differentiation propensity towards definitive endoderm

ABSTRACT: Endogenous suppression of WNT signalling in human embryonic stem cells leads to low differentiation propensity towards definitive endoderm

PROVIDER: PRJNA622953 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11476900.fastq.gz	Fastqsanger.gz
	SRR11476901.fastq.gz	Fastqsanger.gz
	SRR11476902.fastq.gz	Fastqsanger.gz
	SRR11476903.fastq.gz	Fastqsanger.gz
	SRR11476904.fastq.gz	Fastqsanger.gz

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Endogenous suppression of WNT signalling in human embryonic stem cells leads to low differentiation propensity towards definitive endoderm

Project description:We compared a transcriptome of hESC line VUB04 which has a low differentiation propensity towards definitive endoderm with transcriptomes of control hESC lines at the undifferentiated stage and after the 24-hour differentiation towards mesendoderm. The results showed that endogenous suppression of WNT signalling in VUB04 results in an inefficient switch from self-renewal to commitment during the definitive endoderm differentiation. Subsequenlty, we demonstrated that this differentiation disruption can be overcome by increasing the WNT stimulation or by inhibiting the PI3K/AKT signalling at the onset of differentiation.

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Pluripotency Factors Regulate Definitive Endoderm Specification through Eomesodermin

Project description:Understanding the molecular mechanisms controlling early cell fate decisions in mammals is a major objective towards the development of robust methods for the differentiation of human pluripotent stem cells into clinically relevant cell types. Here, we used human embryonic stem cells (hESCs) to study specification of definitive endoderm in vitro. Using a combination of whole genome expression and ChIP-seq analyses, we established a hierarchy of transcription factors regulating endoderm specification. Importantly, pluripotency factors, namely NANOG, OCT4 and SOX2 have an essential function in this network by actively directing differentiation. Indeed, these transcription factors control the expression of EOMES, which marks the onset of endoderm specification. In turn, EOMES interacts with SMAD2/3 to initiate the transcriptional network governing endoderm formation. Together, these results provide for the first time a comprehensive molecular model connecting the transition from pluripotency to endoderm specification during mammalian development. ChIP-Seq of Eomesodermin binding in human embyonic stem cells, differentiated towards an endodermal fate for 48h in chemically-defined culture media. Includes an input DNA control. Supplementary file GSE26097_README.txt contains descriptions of the raw data files and processed data files.

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Saracatinib Promotes Definitive Endoderm Differentiation by Inhibition of FAK-YAP Signaling Axis

Project description:Optimizing the efficiency of definitive endoderm differentiation is significant for the generation of diverse organ-like structures. In this study, we utilized saracatinib to enhance definitive endoderm differentiation in pluripotent stem cells. We found saracatinib significantly improved the definitive endoderm differentiation at low concentrations. To investigate the impact of 0.5 μM saracatinib on definitive endoderm differentiation of ESC H1 cells, we conducted RNA-seq analysis with differentiated cells with or without 0.5 μM saracatinib treatment.

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Pluripotency Factors Regulate Definitive Endoderm Specification through Eomesodermin

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A distinct microRNA signature for definitive endoderm derived from human embryonic stem cells

Project description:This SuperSeries is composed of the following subset Series: GSE16678: MicroRNA expression data from differentiation of human Cyt49 ESCs into definitive endoderm in feeder-free conditions GSE16681: mRNA expression data from differentiation of human ESCs into definitive endoderm, Cyt49 on matrigel GSE16687: MicroRNA expression data from differentiation of human Cyt49 ESCs into definitive endoderm on MEF feeder layers GSE16689: MicroRNA expression data from differentiation of human H9 ESCs into definitive endoderm on MEF feeder layers Refer to individual Series

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Project description:Eomes related gene regulation in Definitive Endoderm

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mRNA expression data from differentiation of human ESCs into definitive endoderm, Cyt49 on matrigel

Project description:hESCs can differentiate into the three primary embryonic lineages (endoderm, mesoderm, ectoderm) as well as extraembryonic tissues. Definitive endoderm (DE) is the first step into the pathway to endoderm derived tissues: pancreas, liver, gut, lung. We used microarrays to detail the changes in mRNA expression during the transition from pluripotent hESCs into definitive endoderm.

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Project description:Precisely co-ordinated activation of lineage specific transcription factors direct cell fate decisions during mouse early development. The T-box transcription factor Eomes is dynamically expressed during mouse gastrulation and is a key regulator of the anterior visceral endoderm (AVE), cardiac mesoderm and definitive endoderm (DE) lineages. The cis-acting regulatory elements that direct spatiotemporally restricted Eomes expression domains have yet to be elucidated. To understand transcriptional regulation of Eomes in Definitive Endoderm open chromatin data was generated by ATAC-seq and histone modifications identified by ChIP-seq. Interactions at the Eomes locus and the loci of two related transcription factors Foxa2 and Lhx1, was also determined by NG Capture-C.

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