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Human stem cell-derived pancreatic acini-like and duct-like organoids demonstrate lineage-specific differences to oncogene activation

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE169008 | GEO | 2021/04/16

REPOSITORIES: GEO

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