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Single cell RNA-seq defines novel heterogeneity within the pancreatic ductal tree

ABSTRACT: Single cell RNA-seq defines novel heterogeneity within the pancreatic ductal tree

PROVIDER: PRJNA668391 | ENA |

REPOSITORIES: ENA

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Single cell RNA-seq defines novel heterogeneity within the pancreatic ductal tree

Project description:Lineage tracing using genetically engineered mouse models has become an essential tool for investigating cell-fate decisions of progenitor cells and biology of mature cell types, with respect to physiology and disease progression. To study disease development, an inventory of an organ’s cell types and understanding of physiologic function is paramount. Here, we performed single-cell RNA sequencing to examine heterogeneity of murine pancreatic duct cells, pancreatobiliary cells, and intrapancreatic bile duct cells. We isolated duct cells within the murine pancreas using the DBA lectin sorting strategy that labels all pancreatic duct cell types. Our data contest the paradigm suggested by previous single cell studies that murine pancreatic duct cells are homogenous. We describe an epithelial mesenchymal transitory axis among our two subpopulations of pancreatic duct cells and identify SPP1 as a regulator of this phenotype and human duct cell de-differentiation. Our results further define functional heterogeneity of pancreatic duct subpopulations by elucidating a role for Geminin in accumulation of DNA damage in the setting of chronic pancreatitis. Our findings implicate diverse functional roles for subpopulations of pancreatic duct cells in disease progression and establish a comprehensive road map of murine pancreatic duct cell, pancreatobiliary cell, and intrapancreatic bile duct cell homeostasis.

2021-02-28 | GSE159343 | GEO

Single-cell transcriptome analysis defines heterogeneity of the murine pancreatic ductal tree.

Project description: Not available

| S-EPMC8184217 | biostudies-literature

A single cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis.

Project description:Pancreatic ducts form an intricate network of tubules that secrete bicarbonate and drive acinar secretions into the duodenum. This network is formed by centroacinar cells, terminal, intercalated, intracalated ducts, and the main pancreatic duct. Ductal heterogeneity at the single-cell level has been poorly characterized. Here, we used scRNA-seq to comprehensively characterize mouse ductal heterogeneity at single-cell resolution of the entire ductal epithelium from centroacinar cells to the main duct. Moreover, we used organoid cultures, injury models and pancreatic tumor samples to interrogate the role of novel ductal populations in pancreas regeneration and exocrine pathogenesis. In our study, we have identified the coexistence of 15 ductal populations within the healthy pancreas and characterized their organoid formation capacity and endocrine differentiation potential. Cluster isolation and subsequent culturing let us identify ductal cell populations with high organoid formation capacity and endocrine and exocrine differentiation potential in vitro, including Wnt-responsive-population, ciliated-population and FLRT3+ cells. Moreover, we have characterized the location of these novel ductal populations in healthy pancreas, chronic pancreatitis and tumor samples, hightlihgting a putative role of WNT-responsive, IFN-responsive and EMT-populations in pancreatic exocrine pathogenesis as their expression inceases in chronic pancreatitis and PanIN lesions. In light of our discovery of previously unidentified ductal populations, we unmask the potential roles of specific ductal populations in pancreas regeneration and exocrine pathogenesis.

2024-03-24 | GSE262292 | GEO

Transcriptional Heterogeneity within the Glucocorticoid Response

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Deconstructive SCNT reveals heterogeneity within Treg population

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Heterogeneity within the PF-EPN-B subgroup

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Systematic comparison of pancreatic ductal adenocarcinoma models identifies a conserved highly plastic basal cell state

Project description:Pancreatic ductal adenocarcinoma (PDAC) portends a dire prognosis. Intra-tumoral heterogeneity and cellular plasticity have emerged as hallmarks of cancer, including PDAC. Yet, our understanding of the mechanisms underpinning cellular diversity in PDAC remains limited. Here, we investigate cellular heterogeneity of PDAC cancer cells across a range of in vitro and in vivo growth conditions using single-cell genomics. We find heterogeneity contracts significantly in 2D and 3D cell culture models but becomes restored upon orthotopic transplantation. Orthotopic transplants reproducibly acquire cell states identified in autochthonous PDAC tumors, including a basal state exhibiting co-expression and co-accessibility of epithelial and mesenchymal genes. Using linage-tracing combined with single-cell transcriptomics, we demonstrate basal cells display high plasticity in situ. This work defines the impact of cellular growth conditions on phenotypic diversity and uncovers a highly plastic cell state with the capacity to facilitate state transitions and promote intra-tumoral heterogeneity in PDAC.

2022-07-25 | GSE209599 | GEO

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