Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DNA methylation profiles of human embryonic stem cells (HUES8) differentiated to pancreatic duct-like organoids.

ABSTRACT: To investigate Keratin 19 (KRT19) expression dynamics in pancreatic development, we established a human pluripotent stem cell (PSC)-based KRT19-mCherry reporter system in various genetic backgrounds to monitor KRT19 expression from ist endogenous gene locus. A genuine differentiation protocol to generate mature pancreatic duct-like organoids (PDLO) was applied. While KRT19/mCherry expression became evident at early endoderm stage, mCherry signal was present in nearly all cells at pancreatic endoderm (PE) and pancreatic progenitor (PP) stage. Interestingly, despite homogenous KRT19 expression, the mCherry positivity dropped to 50% after ductal maturation, indicating a permanent switch from biallelic to monoallelic expression. DNA methylation profiling separated the distinct differentiation intermediates with site specific DNA methylation patterns occuring at the KRT19 locus during ductal maturation. Accordingly, the monoallelic switch was partially reverted upon treatment with a DNA-methyltransferase inhibitor.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234345 | GEO | 2023/06/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The immunological comparison of control PDA tumors and Krt19-edited PDA tumors

2022-01-07 | GSE193027 | GEO

The immunological comparison of control PDA tumors and Krt19-edited PDA tumors

Project description:Our studies indicate that cancer cells of carcinomas are coated with CXCL12 chemokine in covalent conjugation with keratin-19 (KRT19). Murine pancreatic ductal adenocarcinomas (PDA) formed with Krt19-edited cancer cells lack the CXCL12-coating and are infiltrated with T cells, compared to tumors formed with control sgScramble PDA cells. To probe the immunological role of this CXCL12-coating thoroughly, bulk RNA sequencing of subcutaneous (s/c) murine sgScramble PDA tumors and Krt19-edited PDA tumors were conducted. As comparison, an immunogenic tumor model was also assessed. To do so, s/c sgScramble PDA tumors and PDA tumors formed with sgScramble cells exppressing doxcycline-inducible ovalbumin (icOVA) were harvested and processed for bulk RNA sequencing.

2022-01-04 | GSE192853 | GEO

Transcriptional profiling of early haematopoietic mesoderm and endoderm in differentiating human pluripotent stem cells.

Project description:The aim of this project was to compare the transcriptional profiles of populations of cells derived from human pluripotent stem cells under haematopoietic and endoderm differentiation conditions. We used a reporter line (denoted SOX-RUNX) that carries mCHERRY inserted into the SOX17 locus and GFP inserted into the RUNX1C locus to mark haematopoietic progenitors (Ng et al., Nature Biotechnology, Nov 2016). SOX17 marks both endothelium and early endoderm. SOX17 is absolutely required at all stages of endoderm formation and the gene is also required for normal endothelial formation and subsequent haematopoieisis. We have also shown that RUNX1 is required for all definitive blood cell formation (Bruveris et al., manuscript submitted).

2022-01-22 | GSE125477 | GEO

Metabolic reprogramming is an initial step in pancreatic carcinogenesis that can be targeted to inhibit acinar-to-ductal metaplasia

Project description:<p>Metabolic reprogramming is a hallmark of cancer and is crucial for cancer progression, making it an attractive therapeutic target. Understanding the role of metabolic reprogramming in cancer initiation could help identify prevention strategies. To address this, we investigated metabolism during acinar-to-ductal metaplasia (ADM), the first step of pancreatic carcinogenesis. Glycolytic markers were elevated in ADM lesions compared to normal tissue from human samples. Comprehensive metabolic assessment in three mouse models with pancreas-specific activation of KRAS, PI3K or MEK1 using Seahorse measurements, NMR metabolome analysis, mass spectrometry, isotope tracing and RNA-seq analysis revealed a switch from oxidative phosphorylation to glycolysis in ADM. Blocking the metabolic switch attenuated ADM formation. Furthermore, mitochondrial metabolism was required for de novo synthesis of serine and glutathione but not for ATP production. MYC mediated the increase in GSH intermediates in ADM, and inhibition of GSH synthesis suppressed ADM development. This study thus identifies metabolic changes and vulnerabilities in the early stages of pancreatic carcinogenesis.</p>

2024-05-31 | MTBLS9772 | MetaboLights

Transcriptional profiling of autophagy proficient and compromised cell lines, determined by expression levels of Atg5

Project description:Autophagy is activated in pancreatic ductal adenocarcinoma (PDAC) and is currently being considered a promising therapeutic target in clinical trials. PDAC is a highly lethal disease with incidence rate equalling mortality rate. Main reasons for PDAC lethality are late-stage diagnosis, high agressiveness and metastatic rate, lack of effective treatments as well as specific diagnostic markers. Here we show that varying levels of the Autophagy related gene 5 (Atg5) determine pancreatic tumor formation and malignancy. While homozygous deletion of Atg5 blocks tumor progression in an in vivo model of PDAC, heterozygous deletion increases tumor aggressiveness and metastasis. Further analyses reveal that monoallelic loss of Atg5 affects mitochondrial homeostasis, changes intracellular calcium oscillations, heightens extracellular cathepsin activities , and promotes a pro-tumorigenic inflammatory microenvironment collectively enhancing tumor cell migration, invasion, and metastasis. Future treatments should take into account that variations in the autophagy pathway may have opposing effects on pancreatic tumor load, especially considering the multitude of autophagy inhibitors currently tested in clinical trials.

2018-10-15 | E-MTAB-6275 | biostudies-arrayexpress

TET1 (HUES8 WT hESCs) and DNMT3B (HUES8 WT and HUES8 TET TKO hESCs) ChIP-Seq

Project description:The TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine, which can lead to DNA demethylation. However, direct connections between TET-mediated DNA demethylation and transcriptional output are difficult to establish due to challenges of distinguishing global versus locus-specific effects. Here we show that TET1/2/3 triple knockout (TKO) human embryonic stem cells (hESCs) exhibit preferential hypermethylation at bivalent promoters without corresponding gene expression changes in undifferentiated hESCs. In the absence of the TET proteins, abnormal accumulation of DNMT3B at bivalent promoters results in hypermethylation and impaired gene activation upon differentiation. Broadly, the competitive balance between the TET proteins and de novo methyltransferases at bivalent promoters could facilitate rapid changes of their methylation state to either activate or silence transcription in a cell-lineage and gene dependent manner.

2017-12-01 | GSE99346 | GEO

Development of lncRNA and Mrna expression signatures for pancreatic ductal adenocarcinoma

Project description:To further development of our lncRNA and mRNA expression approach to pancreatic ductal adenocarcinoma(PDAC), we have employed lncRNA and mRNA microarray expression profiling as a discovery platform to identify lncRNA and mRNA expression in pancreatic ductal adenocarcinoma.Human pancreatic ductal adenocarcinoma tissues and normal pancreatic tissues from PDAC donors and other duodenum diseases donors. analyze mRNA and lncRNA expression in pancreatic ductal adenocarcinoma (PDAC) by microarray platform

2014-11-18 | E-GEOD-57144 | biostudies-arrayexpress

Pancreatic ductal adenocarcinoma

Project description:Pancreatic ductal adenocarcinoma

| PRJNA432344 | ENA

RNA Sequencing of HUES8 WT and HUES8 TET1/2/3 TKO hESCs

2017-12-01 | GSE89726 | GEO

Long-term correction of diabetes in mice by in vivo reprogramming of pancreatic ducts

Project description:Here, we report in vivo reprogramming of pancreatic ductal cells through intra-ductal delivery of an adenoviral vector expressing the transcription factors Pdx1, Neurog3 and Mafa (adPNM). To better understand the extent of reprogramming in induced pancreatic ductal cells, comparative single cell RNA sequencing was performed on insulin+ pancreatic ductal cells and pancreatic β-cells. Compared with pancreatic β cells, we show that insulin+ pancreatic ductal cells had established a β-cell gene expression program, albeit with immature features.

2018-05-01 | GSE109113 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data