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Journal article
Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids
Cell stem cell, v 28(6), pp 1090-1104.e6
03 Jun 2021
PMID: 33915081
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 inmaintaining 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(R201C) induces cystic growth more effectively in ductal than acinar organoids, whereas KRAS(G12D) is more effective in modeling cancer in vivo when expressed in acinar compared with ductal organoids. KRAS(G12D), but not GNAS(R201C), 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.
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Details
- Title
- Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids
- Creators
- Ling Huang - College Station Medical CenterRidhdhi Desai - College Station Medical CenterDaniel N. Conrad - Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USANayara C. Leite - Harvard UniversityDipikaa Akshinthala - College Station Medical CenterChristine Maria Lim - College Station Medical CenterRaul Gonzalez - College Station Medical CenterLakshmi B. Muthuswamy - College Station Medical CenterZev Gartner - Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USASenthil K. Muthuswamy - College Station Medical Center
- Publication Details
- Cell stem cell, v 28(6), pp 1090-1104.e6
- Publisher
- Elsevier
- Number of pages
- 21
- Grant note
- Hirschberg Foundation for Pancreatic Cancer Research R01GM135462 / NIGMS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000658938000013
- Scopus ID
- 2-s2.0-85105042825
- Other Identifier
- 991022035262704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell & Tissue Engineering
- Cell Biology