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Lineage Tracing of Primary Human Pancreatic Acinar and Ductal Cells for Studying Acinar-to-Ductal Metaplasia

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Pancreatic Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1882))

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Abstract

Acinar-to-ductal metaplasia may play important roles in the development of various pancreatic diseases. Here, we describe a method to induce ADM in primary human cells in 3D culture. We developed a flow cytometry lineage tracing strategy to identify and sort viable acinar, ductal, and acinar-derived ductal-like cells for further molecular and functional analysis.

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References

  1. Guney MA, Gannon M (2009) Pancreas cell fate. Birth Defects Res Part C Embryo Today Rev 87:232–248

    Article  CAS  Google Scholar 

  2. Shih HP, Wang A, Sander M (2013) Pancreas organogenesis: from lineage determination to morphogenesis. Annu Rev Cell Dev Biol 29:81–105

    Article  CAS  Google Scholar 

  3. Longnecker D (2014) Anatomy and histology of the pancreas. Pancreapedia. https://doi.org/10.3998/panc.2014.3

  4. Bailey JM, DelGiorno KE, Crawford HC (2014) The secret origins and surprising fates of pancreas tumors. Carcinogenesis 35:1436–1440

    Article  CAS  Google Scholar 

  5. Logsdon CD, Arumugam T, Ramachandran V (2015) Animal Models of Gastrointestinal and Liver Diseases. The difficulty of animal modeling of pancreatic cancer for preclinical evaluation of therapeutics. Am J Physiol Gastrointest Liver Physiol 309:G283–G291

    Article  CAS  Google Scholar 

  6. De La OJ-P, Emerson LL, Goodman JL et al (2008) Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia. Proc Natl Acad Sci U S A 105:18907–18912

    Article  Google Scholar 

  7. Kopp JL, Grompe M, Sander M (2016) Stem cells versus plasticity in liver and pancreas regeneration. Nat Cell Biol 18:238–245

    Article  Google Scholar 

  8. Shi G, DiRenzo D, Qu C et al (2013) Maintenance of acinar cell organization is critical to preventing Kras-induced acinar-ductal metaplasia. Oncogene 32:1950–1958

    Article  CAS  Google Scholar 

  9. Kopp JL, von Figura G, Mayes E et al (2012) Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell 22:737–750

    Article  CAS  Google Scholar 

  10. Means AL, Meszoely IM, Suzuki K et al (2005) Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates. Development 132:3767–3776

    Article  CAS  Google Scholar 

  11. Liou G-Y, Döppler H, Necela B et al (2013) Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-κB and MMPs. J Cell Biol 202:563–577

    Article  CAS  Google Scholar 

  12. Liou G-Y, Döppler H, Braun UB et al (2015) Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia. Nat Commun 6:6200

    Article  Google Scholar 

  13. Chen N-M, Singh G, Koenig A et al (2015) NFATc1 Links EGFR signaling to induction of Sox9 transcription and acinar-ductal transdifferentiation in the pancreas. Gastroenterology 148:1024–1034.e9

    Article  CAS  Google Scholar 

  14. Houbracken I, de Waele E, Lardon J et al (2011) Lineage tracing evidence for transdifferentiation of acinar to duct cells and plasticity of human pancreas. Gastroenterology 141:731–741

    Article  Google Scholar 

  15. Lee J, Sugiyama T, Liu Y et al (2013) Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells. Elife 2:e00940. https://doi.org/10.7554/eLife.00940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Liu J, Akanuma N, Liu C et al (2016) TGF-β1 promotes acinar to ductal metaplasia of human pancreatic acinar cells. Sci Rep 6:30904

    Article  CAS  Google Scholar 

  17. Akanuma N, Liu J, Liou GY et al (2017) Paracrine secretion of transforming growth factor β by ductal cells promotes acinar-to-ductal metaplasia in cultured human exocrine pancreas tissues. Pancreas 46:1202–1207. https://doi.org/10.1097/MPA.0000000000000913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Pei Wang .

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Liu, J., Wang, P. (2019). Lineage Tracing of Primary Human Pancreatic Acinar and Ductal Cells for Studying Acinar-to-Ductal Metaplasia. In: Su, G. (eds) Pancreatic Cancer. Methods in Molecular Biology, vol 1882. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8879-2_5

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  • DOI: https://doi.org/10.1007/978-1-4939-8879-2_5

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8878-5

  • Online ISBN: 978-1-4939-8879-2

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