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An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes [memory + KrasG12D scRNA-seq]

ABSTRACT: An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes [memory + KrasG12D scRNA-seq]

PROVIDER: PRJNA814078 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18274884.fastq.gz	Fastqsanger.gz
	SRR18274885.fastq.gz	Fastqsanger.gz
	SRR18274886.fastq.gz	Fastqsanger.gz
	SRR18274887.fastq.gz	Fastqsanger.gz

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An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes [memory + KrasG12D scRNA-seq]

Project description:An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes [memory + KrasG12D scRNA-seq]

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An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes [Acute Pancreatitis scRNA-seq]

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An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes [bulk ATAC-seq]

Project description:Inflammation is essential to the disruption of tissue homeostasis, and, in the pancreas, can destabilize the identity of terminally differentiated acinar cells. Herein we employ lineage-traced mouse models to delineate the chromatin dynamics that accompany the cycle of metaplasia and regeneration following pancreatitis, and unveil the presence of an epigenetic memory of inflammation in the pancreatic acinar cell compartment. We observe that despite histologic resolution of pancreatitis, acinar cells fail to return to their molecular baseline after several months, representing an incomplete cell fate decision. In vivo, this epigenetic memory controls lineage plasticity, with diminished metaplasia in response to a second inflammatory insult but increased tumorigenesis with an oncogenic Kras mutation. We demonstrate that both persistent chromatin and transcriptional changes constituting memory are recalled with oncogenic stress. Together, our findings define the dynamics and recall of an epigenetic memory of inflammation that impacts cell fate decisions in a context-dependent manner.

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An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes

Project description:An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes

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An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes

Project description:This SuperSeries is composed of the SubSeries listed below.

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An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes [bulk ATAC-seq]

Project description:An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes [bulk ATAC-seq]

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Transcription profiling of pancreata from wild type, KrasG12D, Ela-Tgfa and KrasG12D Ela-Tgfa mice

Project description:Transcription profiling by array of pancreas from KrasG12D, Ela-Tgfa and KrasG12D Ela-Tgfa mice

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An Epigenetic Memory of Inflammation Induces Context-Dependent Lineage Plasticity in the Pancreas with Divergent Phenotypic Outcomes [Acute Pancreatitis scRNA-seq]

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Project description:Experiment designed to study the effect of deregulated myc on pancreatic cancer progression and regression. In the KRasG12D/RosaMycER mouse model KRas and MycER are expressed exclusively in the pancreas, but MycER activity depends on Tamoxifen presence. For this experiment a mouse was treated with Tamoxifen during 3 weeks, the pancreas was collected and the epithelial cells were grown in vitro in the presence of 4-OHT (4-Hydroxytamoxifen, active form of Tamoxifen). RNAseq were preformed on the cell line treated as follows: 1- 4-OHT all the time. 2- EtOH 6h. 3- EtOH 12h. 4- EtOH 18h.

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