Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Extrinsic KRAS signaling shapes the pancreatic microenvironment through fibroblast reprogramming

ABSTRACT: We utilized the inducible and reversible iKras* genetically engineered mouse model to intiate oncogenic Kras (Kras*) expression in the pancreatic epithelium by providing mice with doxycycline water, and then switched mice to regular water thereby turning expression of Kras* off for 3 days, 3 weeks post-induction of acute pancreatitis. Single cell RNA sequencing revealed that fibroblasts are reprogrammed by signals originating from epithelial Kras*-expressing cells to shape the immune microenvironment during pancreatic tumorigenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE179846 | GEO | 2022/02/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Extrinsic KRAS signaling shapes the pancreatic microenvironment through fibroblast reprogramming

Project description:Extrinsic KRAS signaling shapes the pancreatic microenvironment through fibroblast reprogramming

| PRJNA745330 | ENA

In vivo reprogramming drives Kras-induced cancer development [expression]

Project description:Accumulation of genetic mutations is thought to be a primary cause of cancer. However, a set of genetic mutations sufficient for cancer development remains unclear in most cancers, including pancreatic cancer. Here, we examined the effect of in vivo reprogramming on Kras-induced cancer development. We first demonstrate that Kras and p53 mutations are insufficient to induce activation of ERK signaling and cancer development in the pancreas. We next show that short transient expression of reprogramming factors (1-3 days) in pancreatic acinar cells results in repression of acinar cell enhancers and reversible loss of acinar cell properties. Notably, the transient expression of reprogramming factors in Kras mutant mice is sufficient to induce robust and persistent activation of ERK signaling in acinar cells and rapid formation of pancreatic ductal adenocarcinoma (PDAC). In contrast, forced expression of acinar cell-related transcription factors inhibits pancreatitis-induced activation of ERK signaling and development of precancerous lesions in Kras-mutated acinar cells.

2018-05-16 | GSE100840 | GEO

In vivo reprogramming drives Kras-induced cancer development [ChIP-seq]

2018-05-16 | GSE100841 | GEO

Single-cell RNA sequencing from PiKP-785 cancer cells under 4 treatment conditions: Kras* On, Kras* 3d off, Kras* 5d off, and Kras* On off on

Project description:Single-cell RNA sequencing analysis was performed on primary pancreatic ductal adenocarcinoma derrived cell line from PiKP (P48-Cre; R26-rtTa-IRES-EGFP; tetO-LSL-KrasG12D/+; Trp53L/L) murine tumors. In this study we establish that oncogenic Kras is the predominant driver of T cell paucity and myeloid infiltration in the pancreatic tumor microenvironment. Then, we use scRNA seq analysis of cultured PiKP cells with and without Kras* extinction to identify immune related genes involved in driving Kras* mediated immune supression in PDAC.

2023-07-22 | GSE201887 | GEO

Epithelial memory of resolved inflammation limits tissue damage while promoting pancreatic tumorigenesis [scRNA-Seq]

Project description:Inflammation is a major risk factor for pancreatic ductal adenocarcinoma (PDAC). When occurring in the context of pancreatitis, mutations of KRAS accelerate tumor development. We discovered that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, epithelial cells of the pancreas display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such adaptation enables the prompt reactivation of acinar-to-ductal metaplasia (ADM) upon subsequent inflammatory events, thus efficiently limiting tissue damage via rapid decrease of zymogen production. We propose that since activating mutations of KRAS maintain an irreversible ADM, they may be beneficial and under strong positive selection in the context of recurrent pancreatitis.

2021-09-17 | GSE181276 | GEO

Epithelial memory of resolved inflammation limits tissue damage while promoting pancreatic tumorigenesis [RNA-seq]

2021-09-17 | GSE180211 | GEO

Epithelial memory of resolved inflammation limits tissue damage while promoting pancreatic tumorigenesis [ChIP-seq]

2021-09-17 | GSE180199 | GEO

Epithelial memory of resolved inflammation limits tissue damage while promoting pancreatic tumorigenesis [ATAC-seq]

2021-09-17 | GSE180192 | GEO

KRAS-induced transcription analysis in immortalized pancreatic cells

Project description:We utilized non-transformed, human pancreatic ductal epithelial (HPDE) cells, previously engineered with the E6 and E7 proteins of the HPV16 virus to emulate loss of p53 and inactivation of the Rb pathway, respectively. Given the frequent activation of KRAS (>90% PDAC tumors) and its early role in pancreatic neoplasia, we sought to engineer HPDE cells containing KRASG12D to provide the appropriate context in which to screen for novel drivers that might represent KRAS effectors. The KRAS-induced transcription analysis was conducted using RNAs extracted from HPDE cells transduced with either control, wild-type KRAS or KRASG12D(pInducer) with or without DOX (100ng/ml) for 72 h, followed by hybridization of labeled cDNA onto Agilent arrays (Agilent G3 Human GE 8x60K) by the Baylor College of Medicine Genome Profiling Core Facility. multi-group comparison

2016-01-19 | E-GEOD-58055 | biostudies-arrayexpress

Determining the KRAS-regulated kinome in PDAC

Project description:Oncogenic KRAS drives cancer growth by activating diverse signaling networks, not all of which have been fully delineated. We set out to establish a system-wide profile of the KRAS-regulated kinase signaling network (kinome) in KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). We knocked down KRAS expression in a panel of six cell lines, and then applied Multiplexed Inhibitor Bead/Mass Spectrometry (MIB/MS) chemical proteomics to monitor changes in kinase activity and/or expression. We hypothesized that depletion of KRAS would result in downregulation of kinases required for KRAS-mediated transforming activities, and in upregulation of other kinases that could potentially compensate for the deleterious consequences of the loss of KRAS. We identified 15 upregulated and 13 downregulated kinases in common across the panel. In agreement with our hypothesis, all 15 of the upregulated kinases have established roles as cancer drivers (e.g., SRC, TGFBR1, ILK), and pharmacologic inhibition of the upregulated kinase, DDR1, suppressed PDAC growth. Interestingly, 11 of the 13 downregulated kinases have established driver roles in cell cycle progression, particularly in mitosis (e.g., WEE1, Aurora A, PLK1). Consistent with a crucial role for the downregulated kinases in promoting KRAS-driven proliferation, we found that pharmacologic inhibition of WEE1 also suppressed PDAC growth. The unexpected paradoxical activation of ERK upon WEE1 inhibition led us to inhibit both WEE1 and ERK concurrently, which caused further potent growth suppression and enhanced apoptotic death than WEE1 inhibition alone. We conclude that system-wide delineation of the KRAS-regulated kinome can identify potential therapeutic targets for KRAS-mutant pancreatic cancer.

2022-02-17 | PXD025819 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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