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Animal Models in Diabetes Research pp 303–315Cite as

Lineage Tracing of Pancreatic Stem Cells and Beta Cell Regeneration

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 933))

Abstract

Restoring a functional β cell mass in diabetes patients by β cell transplantation or stimulation of β cell regeneration are promising approaches. It requires knowledge on the mechanisms of β cell neogenesis, an issue that is still quite controversial. Postnatal islet regeneration may or may not depend on an influx of new islet cells from adult progenitors. To solve this issue in animal models, genetic lineage tracing has become a crucial research method. This method allows to test the various hypotheses that have been proposed concerning β cell neogenesis and regeneration.

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References

  1. Keymeulen B, Ling Z, Gorus FK et al (1998) Implantation of standardized beta-cell grafts in a liver segment of IDDM patients: graft and recipients characteristics in two cases of insulin-independence under maintenance immunosuppression for prior kidney graft. Diabetologia 41:452–459

    Article  PubMed  CAS  Google Scholar 

  2. Ryan EA, Lakey JR, Rajotte RV et al (2001) Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes 50:710–719

    Article  PubMed  CAS  Google Scholar 

  3. Shapiro AM, Lakey JR, Ryan EA et al (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343:230–238

    Article  PubMed  CAS  Google Scholar 

  4. Street CN, Lakey JR, Shapiro AM et al (2004) Islet graft assessment in the Edmonton protocol: implications for predicting long-term clinical outcome. Diabetes 53:3107–3114

    Article  PubMed  CAS  Google Scholar 

  5. Warnock GL, Kneteman NM, Ryan EA et al (1992) Long-term follow-up after transplantation of insulin-producing pancreatic islets into patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35:89–95

    Article  PubMed  CAS  Google Scholar 

  6. Butler AE, Janson J, Bonner-Weir S et al (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110

    Article  PubMed  CAS  Google Scholar 

  7. Jurgens CA, Toukatly MN, Fligner CL et al (2011) beta-Cell loss and beta-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition. Am J Pathol 178:2632–2640

    Article  PubMed  CAS  Google Scholar 

  8. Wang RN, Kloppel G, Bouwens L (1995) Duct- to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats. Diabetologia 38:1405–1411

    Article  PubMed  CAS  Google Scholar 

  9. Rooman I, Bouwens L (2004) Combined gastrin and epidermal growth factor treatment induces islet regeneration and restores normoglycaemia in C57Bl6/J mice treated with alloxan. Diabetologia 47:259–265

    Article  PubMed  CAS  Google Scholar 

  10. Solar M, Cardalda C, Houbracken I et al (2009) Pancreatic exocrine duct cells give rise to insulin-producing beta cells during embryogenesis but not after birth. Dev Cell 17:849–860

    Article  PubMed  CAS  Google Scholar 

  11. Nir T, Melton DA, Dor Y (2007) Recovery from diabetes in mice by beta cell regeneration. J Clin Invest 117:2553–2561

    Article  PubMed  CAS  Google Scholar 

  12. Thorel F, Nepote V, Avril I et al (2010) Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature 464:1149–1154

    Article  PubMed  CAS  Google Scholar 

  13. Gu G, Dubauskaite J, Melton DA (2002) Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129:2447–2457

    PubMed  CAS  Google Scholar 

  14. Kawaguchi Y, Cooper B, Gannon M et al (2002) The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 32:128–134

    Article  PubMed  CAS  Google Scholar 

  15. Zhou Q, Law AC, Rajagopal J et al (2007) A multipotent progenitor domain guides pancreatic organogenesis. Dev Cell 13:103–114

    Article  PubMed  CAS  Google Scholar 

  16. Sato T, Vries RG, Snippert HJ et al (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459:262–265

    Article  PubMed  CAS  Google Scholar 

  17. Spangrude GJ, Heimfeld S, Weissman IL (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241:58–62

    Article  PubMed  CAS  Google Scholar 

  18. Barker N, Clevers H (2010) Lineage tracing in the intestinal epithelium. Curr Protoc Stem Cell Biol Chapter 5:Unit5A.4

  19. Ramiya VK, Maraist M, Arfors KE et al (2000) Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 6:278–282

    Article  PubMed  CAS  Google Scholar 

  20. Suzuki A, Nakauchi H, Taniguchi H (2004) Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 53:2143–2152

    Article  PubMed  CAS  Google Scholar 

  21. Rovira M, Scott SG, Liss AS et al (2010) Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas. Proc Natl Acad Sci U S A 107:75–80

    Article  PubMed  CAS  Google Scholar 

  22. Oshima Y, Suzuki A, Kawashimo K et al (2007) Isolation of mouse pancreatic ductal progenitor cells expressing CD133 and c-Met by flow cytometric cell sorting. Gastroenterology 132:720–732

    Article  PubMed  CAS  Google Scholar 

  23. Lardon J, Corbeil D, Huttner WB et al (2008) Stem cell marker prominin-1/AC133 is expressed in duct cells of the adult human pancreas. Pancreas 36:e1–e6

    Article  PubMed  Google Scholar 

  24. Mato E, Lucas M, Petriz J et al (2009) Identification of a pancreatic stellate cell population with properties of progenitor cells: new role for stellate cells in the pancreas. Biochem J 421:181–191

    Article  PubMed  CAS  Google Scholar 

  25. Zulewski H, Abraham EJ, Gerlach MJ et al (2001) Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 50:521–533

    Article  PubMed  CAS  Google Scholar 

  26. Seaberg RM, Smukler SR, Kieffer TJ et al (2004) Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 22:1115–1124

    Article  PubMed  CAS  Google Scholar 

  27. Smukler SR, Arntfield ME, Razavi R et al (2011) The adult mouse and human pancreas contain rare multipotent stem cells that express insulin. Cell Stem Cell 8:281–293

    Article  PubMed  CAS  Google Scholar 

  28. Dor Y, Brown J, Martinez OI et al (2004) Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41–46

    Article  PubMed  CAS  Google Scholar 

  29. Inada A, Nienaber C, Katsuta H et al (2008) Carbonic anhydrase II-positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birth. Proc Natl Acad Sci U S A 105:19915–19919

    Article  PubMed  CAS  Google Scholar 

  30. Bonner-Weir S, Li WC, Ouziel-Yahalom L et al (2010) Beta-cell growth and regeneration: replication is only part of the story. Diabetes 59:2340–2348

    Article  PubMed  CAS  Google Scholar 

  31. Kopinke D, Murtaugh LC (2010) Exocrine-to-endocrine differentiation is detectable only prior to birth in the uninjured mouse pancreas. BMC Dev Biol 10:38

    Article  PubMed  Google Scholar 

  32. Kopp JL, Dubois CL, Schaffer AE et al (2011) Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas. Development 138:653–665

    Article  PubMed  CAS  Google Scholar 

  33. Furuyama K, Kawaguchi Y, Akiyama H et al (2011) Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet 43:34–41

    Article  PubMed  CAS  Google Scholar 

  34. Erickson RP, Grimes J, Venta PJ et al (1995) Expression of carbonic anhydrase II (CA II) promoter-reporter fusion genes in multiple tissues of transgenic mice does not replicate normal patterns of expression indicating complexity of CA II regulation in vivo. Biochem Genet 33:421–437

    Article  PubMed  CAS  Google Scholar 

  35. Parkkila AK, Scarim AL, Parkkila S et al (1998) Expression of carbonic anhydrase V in pancreatic beta cells suggests role for mitochondrial carbonic anhydrase in insulin secretion. J Biol Chem 273:24620–24623

    Article  PubMed  CAS  Google Scholar 

  36. Bouwens L (1998) Transdifferentiation versus stem cell hypothesis for the regeneration of islet beta-cells in the pancreas. Microsc Res Tech 43:332–336

    Article  PubMed  CAS  Google Scholar 

  37. Tosh D, Slack JM (2002) How cells change their phenotype. Nat Rev Mol Cell Biol 3:187–194

    Article  PubMed  CAS  Google Scholar 

  38. Baeyens L, De Breuck S, Lardon J et al (2005) In vitro generation of insulin-producing beta cells from adult exocrine pancreatic cells. Diabetologia 48:49–57

    Article  PubMed  CAS  Google Scholar 

  39. Minami K, Okuno M, Miyawaki K et al (2005) Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells. Proc Natl Acad Sci U S A 102:15116–15121

    Article  PubMed  CAS  Google Scholar 

  40. Baeyens L, Bonne S, Bos T et al (2009) Notch signaling as gatekeeper of rat acinar-to-beta-cell conversion in vitro. Gastroenterology 136:1750–1760 e1713

    Google Scholar 

  41. Baeyens L, Bonne S, German MS et al (2006) Ngn3 expression during postnatal in vitro beta cell neogenesis induced by the JAK/STAT pathway. Cell Death Differ 13:1892–1899

    Article  PubMed  CAS  Google Scholar 

  42. Houbracken I, Waele ED, Lardon J et al (2011) Lineage tracing evidence for transdifferentiation of acinar to duct cells and plasticity of human pancreas. Gastroenterology 141(2):731–741

    Article  PubMed  Google Scholar 

  43. Zhou Q, Brown J, Kanarek A et al (2008) In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455:627–632

    Article  PubMed  CAS  Google Scholar 

  44. Desai BM, Oliver-Krasinski J, De Leon DD et al (2007) Preexisting pancreatic acinar cells contribute to acinar cell, but not islet beta cell, regeneration. J Clin Invest 117:971–977

    Article  PubMed  CAS  Google Scholar 

  45. Xu X, D’Hoker J, Stange G et al (2008) Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 132:197–207

    Article  PubMed  CAS  Google Scholar 

  46. Collombat P, Xu X, Ravassard P et al (2009) The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells. Cell 138:449–462

    Article  PubMed  CAS  Google Scholar 

  47. Chung CH, Hao E, Piran R et al (2010) Pancreatic beta-cell neogenesis by direct conversion from mature alpha-cells. Stem Cells 28:1630–1638

    Article  PubMed  CAS  Google Scholar 

  48. Inada A, Nienaber C, Bonner-Weir S (2006) Endogenous beta-galactosidase expression in murine pancreatic islets. Diabetologia 49:1120–1122

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Cell Differentiation Lab, Vrije Universiteit Brussel, Brussels, Belgium

    Isabelle Houbracken, Iris Mathijs & Luc Bouwens

Authors
  1. Isabelle Houbracken
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  2. Iris Mathijs
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  3. Luc Bouwens
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Corresponding author

Correspondence to Luc Bouwens .

Editor information

Editors and Affiliations

  1. , Department of Pharmacology, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, Nuthetal, 14558, Germany

    Hans-Georg Joost

  2. German Diabetes Centre, Clinical Biochemistry &Pathobiochemistry, Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, Düsseldorf, 40225, Germany

    Hadi Al-Hasani

  3. , Department of Experimental Diabetology, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, Nuthetal, 14558, Germany

    Annette Schürmann

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Houbracken, I., Mathijs, I., Bouwens, L. (2012). Lineage Tracing of Pancreatic Stem Cells and Beta Cell Regeneration. In: Joost, HG., Al-Hasani, H., Schürmann, A. (eds) Animal Models in Diabetes Research. Methods in Molecular Biology, vol 933. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-068-7_20

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  • DOI: https://doi.org/10.1007/978-1-62703-068-7_20

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-067-0

  • Online ISBN: 978-1-62703-068-7

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