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Tuft cell formation reflects epithelial plasticity in pancreatic injury; implications for modeling human pancreatitis

ABSTRACT: We performed RNA-seq on pancreatic tuft cells and non-tuft epithelial cells in caerulein-induced pancreatitis

ORGANISM(S): Mus musculus

PROVIDER: GSE143749 | GEO | 2020/01/16

REPOSITORIES: GEO

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Tuft cell formation reflects epithelial plasticity in pancreatic injury; implications for modeling human pancreatitis

Project description:Tuft cell formation reflects epithelial plasticity in pancreatic injury; implications for modeling human pancreatitis

| PRJNA601477 | ENA

Tuft Cell Formation Reflects Epithelial Plasticity in Pancreatic Injury: Implications for Modeling Human Pancreatitis.

Project description:Chronic pancreatitis, a known risk factor for the development of pancreatic ductal adenocarcinoma (PDA), is a serious, widespread medical condition characterized by inflammation, fibrosis, and acinar to ductal metaplasia (ADM). ADM is a cell type transdifferentiation event where pancreatic acinar cells become ductal-like under conditions of injury or oncogenic mutation. Here, we show that chronic pancreatitis and ADM in genetically wild type mice results in the formation of a significant population of chemosensory tuft cells. Transcriptomic analyses of pancreatitis tuft cells identify expression of inflammatory mediators, consistent with a role for tuft cells in injury progression and/or resolution. Though similar to tuft cell populations in other organs and disease systems, we identified a number of key differences that suggest context-specific tuft cell functions. We evaluated seven different mouse strains for tuft cell formation in response to chronic injury and identified significant heterogeneity reflecting varying proclivity for epithelial plasticity between strains. These results have interesting implications in the role of epithelial plasticity and heterogeneity in pancreatitis and highlight the importance of mouse strain selection when modeling human disease.

| S-EPMC7033634 | biostudies-literature

mRNA expression pattern of KrasG12D mice with acute pancreatitis compared with wild-type mice without acute pancreatitis

Project description:Transgenic KrasG12D mice can recapitulate pancreas intra-epithelial neoplasia (PanIN). Caerulein is a cholecystokinin analogue and induces acute pancreatitis when injected intra-abdominally. Caerulein-induced acute pancreatitis will accelerate PanIN progression in KrasG12D mice. We compared mRNA profile changes between KrasG12D mice with acute caerulein-induced pancreatitis and wild-type mice without acute pancreatitis. The experiment had two groups. Experiment group: KrasG12D mice with acute caerulein-induced pancreatitis (N=6). Three mice in experiment group received 1-week caerulein injection, and the other three mice received 2-week caerulein injection. All experiment group mice started to receive caerulein injection at 1-month of age, and were sacrificed at the last day of caerulein injection. Control group: wild-type mice without acute pancreatitis (N=6). The mice were sacrificed at 1.5-month of age. Whole pancreas tissue lysate samples were subjected to mRNA array assay.

2016-05-14 | E-GEOD-77983 | biostudies-arrayexpress

mRNA expression pattern of KrasG12D mice with acute pancreatitis compared with wild-type mice without acute pancreatitis

2016-05-14 | GSE77983 | GEO

Tuft cells restrain pancreatic tumorigenesis through paracrine eicosanoid signaling [single-cell RNA-seq]

Project description:We performed Smart-seq2 scRNAseq on 156 pancreatic tuft cells . We also profiled FACS sorted EpCAM+;CD45+ immune cells and EpCAM-;CD45- non-immune stroma cells from from 3 caerulein-treated KC and 2 caerulein-treated KPouC pancreata by using the 10X Genomics 3' scRNAseq v3.1 kit.

2020-07-13 | GSE154259 | GEO

Hepatic transcriptome analysis of control, acute pancreatitis and severe acute pancreatitis mice

Project description:Purpose: The purpose of this study was to compare the hepatic transcriptome in the control group, acute pancreatitis, and severe acute pancreatitis, in order to identify metabolic gene changes during pancreatitis. Methods: 6-week Balb/c mice were subjected to AP (caerulein), SAP (caerulein and LPS) and control (saline), and mice liver tissues were harvested at 24 hours for RNA preparation (n=8 each group). Results: Among 11952 mapped genes, 8977 differentially expressed genes were identified by RNA-seq, including 351 genes induced in AP compare to Control and 5249 genes down regulated in SAP compare to AP. The genes up regulated were mainly related to fatty acid oxidation and ketone body synthesis especially Cpt2 and Acadvl, while genes that down regulated were associated with energy metabolism and inflammation. The overlap of two gene sets were 96 genes that involved in fatty acid metabolism. Conclusions: Our study revealed that in AP, genes associated with ketone body synthesis are upregulated in liver, in SAP, fatty acid oxidation related genes are downregulated in liver. Our data revealed the crosstalk between pancreas and liver, illustrated the difference of metabolism in AP and SAP.

2022-04-06 | GSE151927 | GEO

Single-cell analysis reveals fibroblast heterogeneity in chronic pancreatitis

Project description:We used 10x Genomics Single Cell 3’v3.1 scRNA sequencing to investigate the cellular heterogeneity in chronic pancreatitis using pancreases of three CP mice. Mice were induced by daily subcutaneous re-injections of caerulein for 28 days

2022-06-22 | GSE182971 | GEO

Men1 and Daxx loss in a mouse model of chronic pancreatitis

Project description:Gene expression was evaluated by RNA-seq of mouse pancreas 5 days following chronic caerulein-induced pancreatitis. Four different genotypes were evluated: i) wild-type, ii) Men1fl/flPdx1-CreTg, iii) Daxxfl/flPdx1-CreTg iv) Daxxfl/flMen1fl/flPdx1-CreTg.

2020-02-13 | GSE145175 | GEO

Potential regulatory proteins in pancreatitis were screened by proteomics using pancreatic tissues of PRSS1 AP mice

Project description:Humanized PRSS1 transgenic mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were screened by proteomics using pancreatic tissues of PRSS1 AP mice.

2021-09-09 | PXD016651 | Pride

Transcription profiling of mouse pancreas from Mist knockouts vs. wild type treated withcaerulein (induces pancreatitis) or saline controls

Project description:Mouse pancreas from wild type and MistKO animals were induced either with caerulein or saline as control and processed for RNA. Targets from three biological replicates of each were generated and the expression profiles were determined using Affymetrix Mouse Expression chips 430. Comparisons between the sample groups allow the identification of genes with differential expression patterns of genes which might contribute to pancreatitis.

2007-12-15 | E-GEOD-3644 | biostudies-arrayexpress

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