Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spontaneously Evolved Progenitor Niches Escape Yap Oncogene Addiction in Advanced Pancreatic Ductal Adenocarcinomas [Cut&Tag]

ABSTRACT: Lineage plasticity has been proposed as a major source of intratumoral heterogeneity and therapeutic resistance. Employing an inducible genetic engineered mouse model, we illustrate that lineage plasticity enables advanced Pancreatic Ductal Adenocarcinoma (PDAC) tumors to develop spontaneous relapse following elimination of the central oncogenic driver - Yap. Transcriptomic and immunohistochemistry analysis of a large panel of PDAC tumors reveals that within high-grade tumors, small niches of PDAC cells gradually evolve to re-activate pluripotent transcription factors (PTFs), which lessen their dependency on Yap. Comprehensive Cut&Tag analysis demonstrate that although acquisition of PTF expression is coupled with the process of epithelial-to-mesenchymal transition (EMT), PTFs form a core transcriptional regulatory circuitry (CRC) with Jun to overcome Yap dependency, which is distinct from the classic TGFb-induced EMT-TF network. A chemical-genetic screen and follow-up functional studies establish Brd4 as an epigenetic gatekeeper for the PTF-Jun CRC, and strong synergy between BET and Yap inhibitors in blocking PDAC growth.

ORGANISM(S): Mus musculus

PROVIDER: GSE210412 | GEO | 2023/01/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Spontaneously Evolved Progenitor Niches Escape Yap Oncogene Addiction in Advanced Pancreatic Ductal Adenocarcinomas [RNA-Seq]

Project description:Lineage plasticity has been proposed as a major source of intratumoral heterogeneity and therapeutic resistance. Employing an inducible genetic engineered mouse model, we illustrate that lineage plasticity enables advanced Pancreatic Ductal Adenocarcinoma (PDAC) tumors to develop spontaneous relapse following elimination of the central oncogenic driver - Yap. Transcriptomic and immunohistochemistry analysis of a large panel of PDAC tumors reveals that within high-grade tumors, small niches of PDAC cells gradually evolve to re-activate pluripotent transcription factors (PTFs), which lessen their dependency on Yap. Comprehensive Cut&Tag analysis demonstrate that although acquisition of PTF expression is coupled with the process of epithelial-to-mesenchymal transition (EMT), PTFs form a core transcriptional regulatory circuitry (CRC) with Jun to overcome Yap dependency, which is distinct from the classic TGFb-induced EMT-TF network. A chemical-genetic screen and follow-up functional studies establish Brd4 as an epigenetic gatekeeper for the PTF-Jun CRC, and strong synergy between BET and Yap inhibitors in blocking PDAC growth.

2023-03-02 | GSE224566 | GEO

Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2 [MeDIP-seq]

Project description:Pioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer transcription factors. However, critical properties of PTFs are still poorly understood, such as how can these transcription factors selectively recognize cell type-specific binding sites and under which conditions can they initiate chromatin remodelling. Here we show that early endoderm binding sites of the paradigm PTF Foxa2 are epigenetically primed by low levels of active chromatin modifications in embryonic stem cells (ESC). Priming of these binding sites is supported by preferential recruitment of Foxa2 to endoderm binding sites compared to lineage-inappropriate binding sites, when ectopically expressed in ESCs. We further show that binding of Foxa2 is required for chromatin opening during endoderm differentiation. However, increased chromatin accessibility was only detected on binding sites which are synergistically bound with other endoderm transcription factors. Thus, our data suggest that binding site selection of PTFs is directed by the chromatin environment and that chromatin opening requires collaboration of PTFs with additional transcription factors.

2019-07-26 | GSE116261 | GEO

Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2 [RNA-seq low input]

2019-07-26 | GSE116260 | GEO

Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2 [RNA-seq]

2019-07-26 | GSE116259 | GEO

Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2 [ChIP-seq Histone-Modifications]

2019-07-26 | GSE116257 | GEO

Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2 [ATAC-seq]

2019-07-26 | GSE116255 | GEO

Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2 [ChIP-seq Transcription Factors]

2019-07-26 | GSE116258 | GEO

Antithetical NFATc1-Sox2 and p53-miR-200 signalling networks governs pancreatic cancer cell plasticity and tumour progression

Project description:Pancreatic ductal adenocarcinoma (PDAC) cells undergo epithelial mesenchymal transdifferentiation (EMT) in adaption to environmental cues, including inflammation, a process that combines tumour cell dedifferentiation with dissemination and acquisition of stemness features. However, the mechanisms coupling inflammation-induced signalling pathways with EMT and stemness remain largely unknown. Here, we reveal the inflammation-induced transcription factor NFATc1 as a central regulator of pancreatic cancer cell plasticity.

2015-02-10 | E-MTAB-2324 | biostudies-arrayexpress

Dichotomous roles of Arid5a augment the immunosuppressive microenvironment of mesenchymal malignant tumors

Project description:Although mesenchymal subtypes of pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) are known as “immunologically cold” tumors, the molecular link between tumor immune evasiveness and mesenchymal phenotype remains largely unknown. Here, we show that AT-rich interaction domain-containing protein 5a (Arid5a), an RNA-binding protein, is involved in immune evasion in PDAC and CRC mouse models. Mass cytometry demonstrated that in tumors from Arid5a-deficient cells, the infiltration of granulocytic myeloid-derived suppressor cells and regulatory T cells is suppressed, but cytotoxic T-lymphocyte recruitment is enhanced. Mechanistically, Arid5a augmented Ido1 and Ccl2 expression by stabilizing these mRNAs in the PDAC model, but not Ido1 in the CRC model. Furthermore, Arid5a expression was substantially increased in mesenchymal subtypes of PDAC and CRC, mediated by ZEB1, and Arid5a promoted TGF-b-induced and IL6-induced epithelial-mesenchymal transition and acquisition of invasiveness in PDAC model cells. Thus, our findings demonstrate that Arid5a is a promising target for immunotolerant malignant tumors.

2021-04-07 | GSE159967 | GEO

Promoter DNA sequence guides factors that position the +1 nucleosome and facilitate TBP binding [sequencing]

Project description:Here we present evidence that precise positioning of the +1 promoter nucleosome in yeast is critical for efficient TBP binding and pre-initiation complex assembly, and is determined, at least in part, by the action of two key factors, the essential chromatin remodeler RSC and one (or more) of a small set of ubiquitous pioneer transcription factors (PTFs). Despite their widespread co-localization, we show that RSC and PTFs often act independently to generate accessible chromatin. Furthermore, we present evidence that RSC binding, as well as the strength and directionality of its action on nucleosomes, depends upon the arrangement of two specific DNA motifs relative to nearby PTF binding sites. Our results provide insights into how promoter DNA sequence instructs trans-acting factors to precisely control nucleosome architecture and stimulate transcription initiation.

2018-06-01 | GSE98259 | 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