Normal pancreas cells cohort
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00010002007 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Pancreatic acinar cells can dedifferentiate upon tissue injury and acquire ductal characteristics. This acquisition of duct cell features is critical in tumor development. Nevertheless, duct cells themselves are less prone for development of PDAC (pancreatic ductal adenocarcinoma) than dedifferentiated acini. We aimed to clarify which genes are unique for dedifferentiated acini. Mixed exocrine preparations of acinar and duct cells were obtained from human pancreatic donor organs and cultured to induce dedifferentiation. We lineage-labeled and FACS-purified these human dedifferentiated acinar cells and compared them to duct cells from the same donor (n=5).
2021-06-17 | E-MTAB-9386 | biostudies-arrayexpress
Project description:We used single-cell RNA sequencing to profile mouse pancreas across models of acute pancreatitis (AP), recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and oncogenic Kras-driven acute pancreatitis (K-AP, abbreviated APK). We captured both whole-pancreas cell suspensions and FACS-enriched mKate2+ epithelial populations from defined timepoints spanning early injury, recurrent damage, chronic inflammation, and Kras-driven precursor lesion formation. These data characterize acinar and epithelial plasticity and associated microenvironmental remodeling across pancreatitis and Kras-mediated disease initiation. BACKGROUND & AIMS: In response to injury, pancreatic acinar cells undergo acinar-to-ductal metaplasia (ADM), marked by loss of acinar identity and acquisition of ductal features. While ADM can resolve to support tissue repair, it may also persist and serve as a precursor to pancreatic cancer. Whether diverse pancreatic stressors drive a shared or context-specific ADM program remains unclear. We sought to comprehensively define metaplastic responses to clinically relevant exocrine pancreas diseases known to increase cancer risk. METHODS: We profiled ADM and the surrounding microenvironment across mouse models of exocrine disease—including acute, recurrent, and chronic pancreatitis, as well as in the setting of oncogenic Kras—capturing over 300,000 single cells. To enable high-quality transcriptomic profiling in enzyme-rich tissue, we leveraged FixNCut, a method that preserves RNA integrity in the exocrine pancreas. Findings were validated in human pancreas tissue using CosMx spatial transcriptomics. RESULTS: We identify a conserved acinar response across disease contexts that gives rise to previously unrecognized distinct metaplastic states, including a “gateway” ADM population that precedes more advanced metaplastic states marked by complete loss of acinar identity. In pancreatic intraepithelial neoplasia (PanIN) precancerous lesions, we detect classical-like and basal-like states, suggesting that pancreatic cancer subtypes are specified much earlier than previously appreciated. In Kras-mutant tissue, we identify a second wave of inflammation and the emergence of an immunosuppressive niche, coinciding with PanIN formation. CONCLUSIONS: Our findings define a conserved program of acinar plasticity across exocrine pancreas diseases. We further link unresolved ADM to immune remodeling during precursor lesion formation and observe the emergence of pancreatic cancer subtypes in early PanIN lesions.
2025-12-22 | GSE314765 | GEO
Project description:The exocrine compartment of the pancreas consisting of ducts and acini makes up most of the pancreatic tissue and is the site of origin for pancreatitis and pancreatic ductal adenocarcinoma (PDAC). Our understanding of the initiation and progression of human PDAC is limited because of challenges associated with maintaining acinar cells in culture. Here we report the commitment of human pluripotent stem cells towards pancreatic duct-like and acini-like organoids that express properties of the neonatal exocrine pancreas. The expression of PDAC-oncogenes KRasG12D or GNASR201C induced cell lineage-specific effects where GNASR201C was more effective in ductal compared to acinar organoids. KRasG12D was more effective in modeling cancer in vivo when expressed in acinar cells and was associated with acinar to ductal metaplastic changes in culture and in vivo. Thus we demonstrate lineage tropism and plasticity in the human exocrine pancreas and identify a renewable source of ductal and acinar epithelia for understanding exocrine development and diseases.
2021-04-16 | GSE169008 | GEO
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
Project description:Acinar and ductal cells are the major epithelial cell types in the exocrine pancreas, but which of these serves as the cell-of-origin in human PDAC has been debated. Our mouse models have demonstrated that oncogenic Kras expression and Trp53 loss in pancreatic acinar or ductal cells can lead to pancreatic cancer. Here, we performed gene expression profiling of bulk acinar cell-derived and ductal cell-derived mouse pancreatic tumors to identify the transcriptomic profiles.
2021-01-05 | GSE164180 | GEO
Project description:Aberrant acinar to ductal metaplasia (ADM), one of the earliest events involved in exocrine pancreatic cancer development, is typically studied using pancreata from transgenic mouse models. We used primary, human pancreatic acinar cells to evaluate the transcriptional profile during the course of ADM.
2022-06-01 | GSE179248 | GEO
Project description:Flow-sorted pancreatic acinar and ductal cells from fresh human pancreatic exocrine tissue were subjected to molecular characterization to identify lineage-specific expression and epigenetic properties. Cells of both lineages were cultured and transformed via lentiviral mutation to form pancreatic ductal adenocarcinoma.
2026-01-01 | GSE222989 | GEO
Project description:Flow-sorted pancreatic acinar and ductal cells from fresh human pancreatic exocrine tissue were subjected to molecular characterization to identify lineage-specific expression and epigenetic properties. Cells of both lineages were cultured and transformed via lentiviral mutation to form pancreatic ductal adenocarcinoma.
2026-01-01 | GSE222988 | GEO
Project description:Flow-sorted pancreatic acinar and ductal cells from fresh human pancreatic exocrine tissue were subjected to molecular characterization to identify lineage-specific expression and epigenetic properties. Cells of both lineages were cultured and transformed via lentiviral mutation to form pancreatic ductal adenocarcinoma.
2023-11-27 | GSE223153 | GEO
Project description:Flow-sorted pancreatic acinar and ductal cells from fresh human pancreatic exocrine tissue were subjected to molecular characterization to identify lineage-specific expression and epigenetic properties. Cells of both lineages were cultured and transformed via lentiviral mutation to form pancreatic ductal adenocarcinoma.
2023-11-27 | GSE222990 | GEO