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Arid1a restrains Kras-dependent changes in acinar cell identity

ABSTRACT: Arid1a restrains Kras-dependent changes in acinar cell identity

PROVIDER: PRJNA471811 | ENA |

REPOSITORIES: ENA

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Arid1a restrains Kras-dependent changes in acinar cell identity

Project description:Arid1a restrains Kras-dependent changes in acinar cell identity

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Arid1a restrains Kras-dependent changes in acinar cell identity

Project description:Mutations in members of the SWI/SNF chromatin remodeling family are common events in human cancer, but the mechanisms whereby disruption of SWI/SNF components alters tumorigenesis remain poorly understood. To model the effect of loss of function mutations in the SWI/SNF subunit Arid1a in pancreatic ductal adenocarcinoma (PDAC) initiation, we directed shRNA triggered, inducible and reversible suppression of Arid1a to the pancreas of mice in the setting of oncogenic KrasG12D. Arid1a cooperates with Kras in the adult pancreas as postnatal silencing of Arid1a following sustained KrasG12D expression induces rapid and irreversible reprogramming of acinar cells into mucinous PDAC precursor lesions. In contrast, Arid1a silencing during embryogenesis, concurrent with KrasG12D activation, leads to retention of acinar cell fate. Together, our results demonstrate Arid1a as a critical modulator of Kras-dependent changes in acinar cell identity, and underscore an unanticipated influence of timing and genetic context on the effects of SWI/SNF complex alterations in epithelial tumorigenesis.

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Arid1a restrains Kras-dependent changes in acinar cell identity.

Project description: Not available

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Genome-wide maps of H3K27ac ocupancy on chromatin in murine acinar cell line upon EGF treatment and Arid1a silencing

Project description:Chromatin Immunoprecipitation-based sequencing (ChIP-seq) of H3K27ac was conduced in murine Kras-mutant acinar cell line 266-6 in the context of Arid1a-knockdown and/or EGF treatment. We found EGFR signaling activation as well as Arid1a silencing leads to additional increase of H3K27ac level genome-widely. And the maximal H3K27ac was achieved by the combined- EGF treatment and Arid1a knockdown.

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SWI/SNF component ARID1A restrains pancreatic neoplasia formation [ChIP-seq]

Project description:ARID1A restrains the formation of PanIN, pancreas ductal adenocarcinoma, and intraductal mucinous neoplasms

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SWI/SNF component ARID1A restrains pancreatic neoplasia formation [RNA-seq]

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Transcriptome analysis of murine primary pancreatic acinar cells in the context of Arid1a deficiency

Project description:mRNA expression profiles were generated from primary pancreatic acinar cells of Arid1a-deficient and Arid1a-wildtype mice. Arid1a depletion leads to transcription activation to the majority of genes.

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Analysis of chromatin accessibility in Arid1a-deficient murine primary pancreatic acinar cells using ATAC-seq

Project description:To gain insight into how the loss of SWI/SNF component ARID1A affects the chromatin accessibility, primary acinar cells were isolated from Arid1a-knockout and control mice and subjected to ATAC-sequencing.

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SWI/SNF component ARID1A restrains pancreatic neoplasia formation

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