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In the Setting of Beta Cell Stress, the Pancreatic Duct Gland Transcriptome shows Characteristics of an Activated Regenerative Response

ABSTRACT: The pancreatic duct gland (PDG) compartment has been proposed as a potential stem cell niche. Little is known of the molecular signature of the PDG compartment in either a quiescent state or the potentially activated state during beta cell stress characteristic of diabetes.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE117679 | GEO | 2019/07/25

REPOSITORIES: GEO

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In the Setting of Beta Cell Stress, the Pancreatic Duct Gland Transcriptome shows Characteristics of an Activated Regenerative Response

Project description:In the Setting of Beta Cell Stress, the Pancreatic Duct Gland Transcriptome shows Characteristics of an Activated Regenerative Response

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Project description:Creating in vitro models of diseases of the pancreatic ductal compartment requires a comprehensive understanding of the developmental trajectories of pancreas-specific cell types. Here, we report the single-cell characterization of the differentiation of pancreatic duct-like organoids (PDLOs) from human induced pluripotent stem cells (hiPSCs) on a microwell chip that facili-tates the uniform aggregation and chemical induction of hiPSC-derived pancreatic progenitors. Using time-resolved single-cell transcriptional profiling and immunofluorescence imaging of the forming PDLOs, we identified differentiation routes from pan-creas progenitors through ductal intermediates to two types of mature duct-like cell and a few non-ductal cell types. PDLO subpopulations expressed either mucins or the cystic fibrosis transmembrane conductance regulator, and resembled human adult duct cells. We also used the chip to uncover ductal markers relevant to pancreatic carcinogenesis, and to establish PDLO co-cultures with stellate cells, which allowed for the study of epithelial–mesenchymal signalling. The PDLO microsystem could be used to establish patient-specific pancreatic duct models.

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