Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33915081.
- Also identified by DOI 10.1016/j.stem.2021.03.022 and PMC identifier 8202734.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The exocrine pancreas, consisting of ducts and acini, is the site of origin of pancreatitis and pancreatic ductal adenocarcinoma (PDAC). Our understanding of the genesis and progression of human pancreatic diseases, including PDAC, is limited because of challenges in maintaining human acinar and ductal cells in culture. Here we report induction of human pluripotent stem cells toward pancreatic ductal and acinar organoids that recapitulate properties of the neonatal exocrine pancreas. Expression of the PDAC-associated oncogene GNAS<sup>R201C</sup> induces cystic growth more effectively in ductal than acinar organoids, whereas KRAS<sup>G12D</sup> is more effective in modeling cancer in vivo when expressed in acinar compared with ductal organoids. KRAS<sup>G12D</sup>, but not GNAS<sup>R201C</sup>, induces acinar-to-ductal metaplasia-like changes in culture and in vivo. We develop a renewable source of ductal and acinar organoids for modeling exocrine development and diseases and demonstrate lineage tropism and plasticity for oncogene action in the human pancreas.
Medical subject headings
- Carcinoma, Pancreatic Ductal
- Pancreas, Exocrine
- Pancreatic Neoplasms