期刊
EMBO JOURNAL
卷 32, 期 20, 页码 2708-2721出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2013.204
关键词
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资金
- MH [EU/236954]
- SFB [EU/232814]
- JHvE [Ti Pharma/T3-106]
- PB (EMBO fellowship)
- HH [EU-HEALTH-F5-2009-241883]
- Dutch Diabetes Foundation [2007.16.001]
- NFSR [G000609N10]
- NIH [1U01DK089571-01]
- Innovative Medicines Initiative Joint Undertaking under grant agreement [155005]
- European Union's Seventh Framework Programme
- EFPIA companies in kind contribution)
- DON Foundation
- Dutch Diabetes Research Foundation
- Rosetrees Trust [M362] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [24689036] Funding Source: KAKEN
Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt-agonistic R-spondins (RSPOs). Intestinal, stomach and liver Lgr5(+) stem cells grow in 3D cultures to form ever-expanding organoids, which resemble the tissues of origin. Wnt signalling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by partial duct ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1-based cultures, and develop into budding cyst-like structures (organoids) that expand five-fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality.
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