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

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

PROVIDER: PRJNA815980 | ENA |

REPOSITORIES: ENA

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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]

2023-10-24 | GSE198184 | GEO

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

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

2023-10-24 | GSE198183 | GEO

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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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]

| PRJNA814078 | ENA

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

Project description: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.

2023-10-24 | GSE198563 | GEO

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.

2023-10-24 | GSE198564 | GEO

An epigenetic memory of inflammation controls context-dependent lineage plasticity in the pancreas [bulk RNA-seq]

2023-10-24 | GSE198558 | GEO

An epigenetic memory of inflammation controls context-dependent lineage plasticity in the pancreas [bulk RNA-seq]

Project description:An epigenetic memory of inflammation controls context-dependent lineage plasticity in the pancreas [bulk RNA-seq]

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Fibrosis induced by resident macrophages has divergent roles in pancreas inflammatory injury and PDAC

Project description:Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages. Whether TRMs and monocyte-derived macrophages have district roles under differing pathologies is not understood. Here, we showed that a substantial portion of the macrophages that accumulated during pancreatitis and pancreatic cancer in mice had expanded from TRMs. Pancreas TRMs had an extracellular matrix remodeling phenotype that was important for maintaining tissue homeostasis during inflammation. Loss of TRMs led to exacerbation of severe pancreatitis and death, due to impaired acinar cell survival and recovery. During pancreatitis, TRMs elicited protective effects by triggering the accumulation and activation of fibroblasts, which was necessary for initiating fibrosis as a wound healing response. The same TRM-driven fibrosis, however, drove pancreas cancer pathogenesis and progression. Together, these findings indicate that TRMs play divergent roles in the pathogenesis of pancreatitis and cancer through regulation of stromagenesis.

2023-06-29 | GSE203005 | GEO

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