Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-seq of mouse cell lines isolated from genetically engineered mouse models of extrahepatic cholangiocarcinoma and pancreatic cancer

ABSTRACT: Biliary tract cancer (BTC) ranks among the most lethal human malignancies, thereby representing an unmet clinical need. In this study, we find that the Pdx1-positive extrahepatic biliary epithelium is highly susceptible towards transformation by activated Pik3caH1047R, but completely refractory to oncogenic KrasG12D. Using genome-wide in vivo piggyBac transposon-based forward genetic screening and genetic loss-of-function experiments, we discover important extrahepatic cholangiocarcinoma (ECC) cancer genes and find that PI3K-signaling output strength and repression of the tumor suppressor p27Kip1 are critical context-specific determinants of tumor formation. This contrasts the pancreas, where oncogenic Kras in concert with Trp53 loss of function are key cancer drivers. Notably, inactivation of p27Kip1 permits KrasG12D-driven ECC development, and bypasses oncogene-induced senescence without triggering the Trp53 pathway. These studies provide a mechanistic link between PI3K-signaling, tissue-specific tumor suppressor barriers, and ECC pathogenesis, and present a novel genetic model of autochthonous ECC and genes driving this highly lethal tumor-subtype.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Mus musculus

SUBMITTER: Chiara Falcomatà

PROVIDER: E-MTAB-10515 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

RNA-seq of pancreatic mouse tumor cell lines

Project description:KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) is highly immunosuppressive and resistant to targeted therapies, immune checkpoint blockade and engineered T cells. In this study, we performed a systematic high throughput combinatorial drug screen and identified a synergistic interaction between the MEK inhibitor trametinib and the multi-kinase inhibitor nintedanib. Using bulk and single-cell RNA sequencing and immunophenotyping, we show that the combination therapy reprograms the immunosuppressive microenvironment and primes cytotoxic and memory T cells to infiltrate the tumors, thereby sensitizing mesenchymal PDAC to PD-L1 inhibition.

2021-11-29 | E-MTAB-11187 | biostudies-arrayexpress

RNA-Seq of explanted murine pancreatic acinar cells

Project description:To investigate the underlying changes during acinar-to-ductal metaplasia, pancreatic acinar cells were isolated from 5 week old KrasG12D-mice. RNA was isolated immediately after isolation (t=0 days) or after 3 days embedded in collagen.

2023-03-02 | E-MTAB-9878 | biostudies-arrayexpress

RNA-Seq of pancreatic tissue from wt, KrasG12D, Pi3kCAH1047R and Mek1dd mice, at 10 weeks and after induction of acute pancreatitis

Project description:To investigate the underlying changes during acinar-to-ductal metaplasia induced by different oncogenes and by acute pancreatitis, pancreatic tissue was isolated from 10 week old control wt, KrasG12D, Pi3kCAH1047R and Mek1dd mice and from mice of the same genotypes after induction of acute pancreatitis.

2024-04-06 | E-MTAB-13946 | biostudies-arrayexpress

RNA-Seq of explanted murine pancreatic acinar cells from wt, KrasG12D, Pi3kCAH1047R and Mek1dd mice

Project description:To investigate the underlying changes during acinar-to-ductal metaplasia induced by different factos, pancreatic acinar cells were isolated from 5 week old wt, KrasG12D, Pi3kCAH1047R and Mek1dd mice. Acinar cells from wt mice were treated with medium (control), Tgfa or IL17a. RNA was isolated immediately after isolation (t=0 days) or after 2-3 days embedded in collagen.

2024-05-31 | E-MTAB-11913 | biostudies-arrayexpress

Gene expression profiling of ampullary carcinomas classifies ampullary carcinomas into biliary-like and intestinal-like subtypes that are prognostic of outcome

Project description:Adenocarcinomas of the ampulla of Vater are classified as biliary cancers, though the exact epithelium of origin for these cancers is not known. We sought to molecularly classify ampullary adenocarcinomas in comparison to known adenocarcinomas of the pancreas, extrahepatic bile duct, and duodenum by gene expression analysis. We analyzed 32 fresh-frozen resected, untreated periampullary adenocarcinomas (8 pancreatic, 2 extrahepatic biliary, 8 duodenal, and 14 ampullary) using the Affymetrix U133 Plus 2.0 genome array.

2013-01-01 | E-GEOD-39409 | biostudies-arrayexpress

Comparison of extrahepatic cholangiocyte organoids and freshly isolated common bile duct cholangiocytes

Project description:Despite the impact of bile duct disorders, treatment options remain very limited. Poor access to biliary tissue and restrictions in long-term culture or significant expansion of primary cholangiocytes have posed major challenges for research in the field. These limitations have so far precluded large scale experiments such as transcriptomic and genome-wide analyses which are urgently needed to better understand biliary physiology and pathophysiology. To address this issue, we have developed a novel system for the isolation and propagation of primary cholangiocytes from the extrahepatic bile ducts. The resulting Extrahepatic Cholangiocyte Organoids (ECOs) maintain their genetic stability, transcriptomic profile and function over long term culture and are compatible with regenerative medicine applications such as biliary reconstruction. We established a novel protocol for the isolation and propagation of primary cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs). The aim of this experiment was to provide in depth characterisation of the transcriptome of ECOs during long term culture. We compare the transcriptome of ECOs cultured for 1 passage (P1), 10 passages (P10) and 20 passages (P20) with freshly isolated primary cholangiocytes from the common bile duct. Embryonic Stem Cells (ES) cells are used as a negative control=

2017-07-04 | E-MTAB-4591 | biostudies-arrayexpress

Simultaneous activation of Kras-Akt and Notch pathways induces extrahepatic biliary cancer via mTORC1 pathway

Project description:Biliary tract cancer (BTC) has poor prognosis. The Notch receptor is aberrantly expressed in extrahepatic cholangiocarcinoma (eCCA). However, the role of Notch signaling in the initiation and progression of eCCA and gallbladder (GB) cancer remains unknown. We investigated the functional role of Notch signaling during tumorigenesis of the extrahepatic bile duct and GB. We demonstrated that simultaneous activation of the Kras–Akt and Notch pathways in EHBD and GB resulted in the formation of BilINs and biliary cancer in a mouse model. Mechanistically, the Kras/Notch–Myc axis activates mTORC1 through phosphorylation of TSC2 in biliary tumorigenesis.

2023-05-04 | GSE231369 | GEO

Gene Expression of Single Extrahepatic Biliary Cells

Project description:These datasets look at the murine profile of extrahepatic biliary cells, primarily epithelial, in normal conditions and under mosaic Ctnnb1 gain of function.

2023-09-22 | GSE223099 | GEO

Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury

Project description:Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands (PBGs) of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly more than ten-fold dilated PBGs following rhesus rotavirus-mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.

2022-12-05 | GSE220054 | GEO