Skip to main content

Advertisement

SpringerLink
Log in

Ontogenesis of Hepatic and Pancreatic Stem Cells

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

In the embryo, the liver and pancreas exhibit a close developmental relationship. Both tissues arise from neighbouring regions of the developing endoderm. As well as this close developmental relationship, the liver and pancreas can, under certain circumstances, regenerate functional components. Understanding the normal development of the two tissue types and the underlying cellular and molecular mechanisms governing normal development and regeneration is critical to the production of novel therapies for treating liver disease and pancreatic disorders such as diabetes and pancreatitis. Herein we discuss the development of the liver and pancreas from progenitor cells in the embryo and the existence of potential stem cells in the adult tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Lammert, E., Cleaver, O., & Melton, D. (2001). Induction of pancreatic differentiation by signals from blood vessels. Science, 294(5542), 564–567.

    PubMed  CAS  Google Scholar 

  2. Jabs, N., et al. (2008). Reduced insulin secretion and content in VEGF-a deficient mouse pancreatic islets. Experimental and Clinical Endocrinology & Diabetes, 116(Suppl 1), S46–S49.

    CAS  Google Scholar 

  3. Le Douarin, N. M. (1975). An experimental analysis of liver development. Medical Biology, 53(6), 427–455.

    PubMed  CAS  Google Scholar 

  4. Tremblay, K. D., & Zaret, K. S. (2005). Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. Developmental Biology, 280(1), 87–99.

    PubMed  CAS  Google Scholar 

  5. Zaret, K. S. (1996). Molecular genetics of early liver development. Annual Review of Physiology, 58, 231–251.

    PubMed  CAS  Google Scholar 

  6. Lee, C. S., et al. (2005). The initiation of liver development is dependent on Foxa transcription factors. Nature, 435(7044), 944–947.

    PubMed  CAS  Google Scholar 

  7. Martinez-Barbera, J. P., Rodriguez, T. A., & Beddington, R. S. (2000). The homeobox gene Hesx1 is required in the anterior neural ectoderm for normal forebrain formation. Developmental Biology, 223(2), 422–430.

    PubMed  CAS  Google Scholar 

  8. Sosa-Pineda, B., Wigle, J. T., & Oliver, G. (2000). Hepatocyte migration during liver development requires Prox1. Nature Genetics, 25(3), 254–255.

    PubMed  CAS  Google Scholar 

  9. Rossi, J. M., et al. (2001). Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. Genes & Development, 15(15), 1998–2009.

    CAS  Google Scholar 

  10. Ober, E. A., et al. (2006). Mesodermal Wnt2b signalling positively regulates liver specification. Nature, 442(7103), 688–691.

    PubMed  CAS  Google Scholar 

  11. McLin, V. A., Rankin, S. A., & Zorn, A. M. (2007). Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development. Development, 134(12), 2207–2217.

    PubMed  CAS  Google Scholar 

  12. Burke, Z. D., Thowfeequ, S., & Tosh, D. (2006). Liver specification: a new role for Wnts in liver development. Current Biology, 16(17), R688–R690.

    PubMed  CAS  Google Scholar 

  13. Hussain, S. Z., et al. (2004). Wnt impacts growth and differentiation in ex vivo liver development. Experimental Cell Research, 292(1), 157–169.

    PubMed  CAS  Google Scholar 

  14. Yeh, T. H., et al. (2010). Liver-specific beta-catenin knockout mice have bile canalicular abnormalities, bile secretory defect, and intrahepatic cholestasis. Hepatology, 52(4), 1410–1419.

    PubMed  CAS  Google Scholar 

  15. Decaens, T., et al. (2008). Stabilization of beta-catenin affects mouse embryonic liver growth and hepatoblast fate. Hepatology, 47(1), 247–258.

    PubMed  CAS  Google Scholar 

  16. Kim, S. K., Hebrok, M., & Melton, D. A. (1997). Notochord to endoderm signaling is required for pancreas development. Development, 124(21), 4243–4252.

    PubMed  CAS  Google Scholar 

  17. Kim, S. K., et al. (2000). Activin receptor patterning of foregut organogenesis. Genes & Development, 14(15), 1866–1871.

    CAS  Google Scholar 

  18. Jonsson, J., et al. (1994). Insulin-promoter-factor 1 is required for pancreas development in mice. Nature, 371(6498), 606–609.

    PubMed  CAS  Google Scholar 

  19. Wilson, M. E., Scheel, D., & German, M. S. (2003). Gene expression cascades in pancreatic development. Mechanisms of Development, 120(1), 65–80.

    PubMed  CAS  Google Scholar 

  20. Jensen, J. (2004). Gene regulatory factors in pancreatic development. Developmental Dynamics, 229(1), 176–200.

    PubMed  CAS  Google Scholar 

  21. Chakrabarti, S. K., & Mirmira, R. G. (2003). Transcription factors direct the development and function of pancreatic beta cells. Trends in Endocrinology and Metabolism, 14(2), 78–84.

    PubMed  CAS  Google Scholar 

  22. Samson, S. L., & Chan, L. (2006). Gene therapy for diabetes: reinventing the islet. Trends in Endocrinology and Metabolism, 17(3), 92–100.

    PubMed  CAS  Google Scholar 

  23. Watada, H. (2004). Neurogenin 3 is a key transcription factor for differentiation of the endocrine pancreas. Endocrine Journal, 51(3), 255–264.

    PubMed  CAS  Google Scholar 

  24. Notenboom, R. G., et al. (2003). Timing and sequence of differentiation of embryonic rat hepatocytes along the biliary epithelial lineage. Hepatology, 38(3), 683–691.

    PubMed  Google Scholar 

  25. Sandhu, J. S., et al. (2001). Stem cell properties and repopulation of the rat liver by fetal liver epithelial progenitor cells. American Journal of Pathology, 159(4), 1323–1334.

    PubMed  CAS  Google Scholar 

  26. Malhi, H., et al. (2002). Isolation of human progenitor liver epithelial cells with extensive replication capacity and differentiation into mature hepatocytes. Journal of Cell Science, 115(Pt 13), 2679–2688.

    PubMed  CAS  Google Scholar 

  27. Oertel, M., et al. (2006). Cell competition leads to a high level of normal liver reconstitution by transplanted fetal liver stem/progenitor cells. Gastroenterology, 130(2), 507–520. quiz 590.

    PubMed  Google Scholar 

  28. Moreno, E., & Basler, K. (2004). dMyc transforms cells into super-competitors. Cell, 117(1), 117–129.

    PubMed  CAS  Google Scholar 

  29. Strick-Marchand, H., et al. (2004). Bipotential mouse embryonic liver stem cell lines contribute to liver regeneration and differentiate as bile ducts and hepatocytes. Proceedings of the National Academy of Sciences of the United States of America, 101(22), 8360–8365.

    PubMed  CAS  Google Scholar 

  30. Allain, J. E., et al. (2002). Immortalization of a primate bipotent epithelial liver stem cell. Proceedings of the National Academy of Sciences of the United States of America, 99(6), 3639–3644.

    PubMed  CAS  Google Scholar 

  31. Tirnitz-Parker, J. E., et al. (2007). Isolation, culture and immortalisation of hepatic oval cells from adult mice fed a choline-deficient, ethionine-supplemented diet. The International Journal of Biochemistry & Cell Biology, 39(12), 2226–2239.

    CAS  Google Scholar 

  32. Shiojiri, N., Lemire, J. M., & Fausto, N. (1991). Cell lineages and oval cell progenitors in rat liver development. Cancer Research, 51(10), 2611–2620.

    PubMed  CAS  Google Scholar 

  33. Evarts, R. P., et al. (1989). In vivo differentiation of rat liver oval cells into hepatocytes. Cancer Research, 49(6), 1541–1547.

    PubMed  CAS  Google Scholar 

  34. Evarts, R. P., et al. (1987). A precursor-product relationship exists between oval cells and hepatocytes in rat liver. Carcinogenesis, 8(11), 1737–1740.

    PubMed  CAS  Google Scholar 

  35. Matthews, V. B., & Yeoh, G. C. (2005). Liver stem cells. IUBMB Life, 57(8), 549–553.

    PubMed  CAS  Google Scholar 

  36. Alison, M. R., Islam, S., & Lim, S. (2009). Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly. The Journal of Pathology, 217(2), 282–298.

    PubMed  CAS  Google Scholar 

  37. Dorrell, C., et al. (2008). Surface markers for the murine oval cell response. Hepatology, 48(4), 1282–1291.

    PubMed  CAS  Google Scholar 

  38. Offield, M. F., et al. (1996). PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development, 122(3), 983–995.

    PubMed  CAS  Google Scholar 

  39. Gu, G., Dubauskaite, J., & Melton, D. A. (2002). Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development, 129(10), 2447–2457.

    PubMed  CAS  Google Scholar 

  40. Herrera, P. L. (2000). Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages. Development, 127(11), 2317–2322.

    PubMed  CAS  Google Scholar 

  41. Gradwohl, G., et al. (2000). Neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proceedings of the National Academy of Sciences of the United States of America, 97(4), 1607–1611.

    PubMed  CAS  Google Scholar 

  42. Gittes, G. K., et al. (1996). Lineage-specific morphogenesis in the developing pancreas: role of mesenchymal factors. Development, 122(2), 439–447.

    PubMed  CAS  Google Scholar 

  43. Miralles, F., Czernichow, P., & Scharfmann, R. (1998). Follistatin regulates the relative proportions of endocrine versus exocrine tissue during pancreatic development. Development, 125(6), 1017–1024.

    PubMed  CAS  Google Scholar 

  44. Percival, A. C., & Slack, J. M. (1999). Analysis of pancreatic development using a cell lineage label. Experimental Cell Research, 247(1), 123–132.

    PubMed  CAS  Google Scholar 

  45. Castaing, M., et al. (2001). Blood glucose normalization upon transplantation of human embryonic pancreas into beta-cell-deficient SCID mice. Diabetologia, 44(11), 2066–2076.

    PubMed  CAS  Google Scholar 

  46. Castaing, M., et al. (2005). Ex vivo analysis of acinar and endocrine cell development in the human embryonic pancreas. Developmental Dynamics, 234(2), 339–345.

    PubMed  CAS  Google Scholar 

  47. Scharfmann, R., et al. (2008). Beta cells within single human islets originate from multiple progenitors. PLoS One, 3(10), e3559.

    PubMed  Google Scholar 

  48. Deutsch, G., et al. (2001). A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development, 128(6), 871–881.

    PubMed  CAS  Google Scholar 

  49. Burke, Z., & Oliver, G. (2002). Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm. Mechanisms of Development, 118(1–2), 147–155.

    PubMed  CAS  Google Scholar 

  50. Takenaga, M., Fukumoto, M., & Hori, Y. (2007). Regulated Nodal signaling promotes differentiation of the definitive endoderm and mesoderm from ES cells. Journal of Cell Science, 120(Pt 12), 2078–2090.

    PubMed  CAS  Google Scholar 

  51. Bone, H. K., et al. (2011). A novel chemically directed route for the generation of definitive endoderm from human embryonic stem cells based on inhibition of GSK-3. Journal of Cell Science, 124(Pt 12), 1992–2000.

    PubMed  CAS  Google Scholar 

  52. Wang, X., et al. (2011). Hepatocytic differentiation of rhesus monkey embryonic stem cells promoted by collagen gels and growth factors. Cell Biology International, 35(8), 775–781.

    PubMed  CAS  Google Scholar 

  53. Gouon-Evans, V., et al. (2006). BMP-4 is required for hepatic specification of mouse embryonic stem cell-derived definitive endoderm. Nature Biotechnology, 24(11), 1402–1411.

    PubMed  CAS  Google Scholar 

  54. Kroon, E., et al. (2008). Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nature Biotechnology, 26(4), 443–452.

    PubMed  CAS  Google Scholar 

  55. D’Amour, K. A., et al. (2006). Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nature Biotechnology, 24(11), 1392–1401.

    PubMed  Google Scholar 

  56. Zhang, D., et al. (2009). Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Research, 19(4), 429–438.

    PubMed  CAS  Google Scholar 

  57. Cai, J., et al. (2010). Generation of homogeneous PDX1(+) pancreatic progenitors from human ES cell-derived endoderm cells. Journal of Molecular Cell Biology, 2(1), 50–60.

    PubMed  CAS  Google Scholar 

  58. Sekiya, S., & Suzuki, A. (2011). Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature, 475(7356), 390–393.

    PubMed  CAS  Google Scholar 

  59. Huang, P., et al. (2011). Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature, 475(7356), 386–389.

    PubMed  CAS  Google Scholar 

  60. Fausto, N. (2004). Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells. Hepatology, 39(6), 1477–1487.

    PubMed  Google Scholar 

  61. Michalopoulos, G. K., & DeFrances, M. C. (1997). Liver regeneration. Science, 276(5309), 60–66.

    PubMed  CAS  Google Scholar 

  62. Overturf, K., et al. (1997). Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes. American Journal of Pathology, 151(5), 1273–1280.

    PubMed  CAS  Google Scholar 

  63. Theise, N. D., et al. (1999). The canals of Hering and hepatic stem cells in humans. Hepatology, 30(6), 1425–1433.

    PubMed  CAS  Google Scholar 

  64. Roskams, T. A., et al. (2004). Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers. Hepatology, 39(6), 1739–1745.

    PubMed  Google Scholar 

  65. Alison, M. R., et al. (1996). Liver damage in the rat induces hepatocyte stem cells from biliary epithelial cells. Gastroenterology, 110(4), 1182–1190.

    PubMed  CAS  Google Scholar 

  66. Crosby, H. A., Kelly, D. A., & Strain, A. J. (2001). Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium. Gastroenterology, 120(2), 534–544.

    PubMed  CAS  Google Scholar 

  67. Dabeva, M. D., et al. (1997). Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver. Proceedings of the National Academy of Sciences of the United States of America, 94(14), 7356–7361.

    PubMed  CAS  Google Scholar 

  68. Rao, M. S., Subbarao, V., & Reddy, J. K. (1986). Induction of hepatocytes in the pancreas of copper-depleted rats following copper repletion. Cell Differentiation, 18(2), 109–117.

    PubMed  CAS  Google Scholar 

  69. Furuyama, K., et al. (2011). Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nature Genetics, 43(1), 34–41.

    PubMed  CAS  Google Scholar 

  70. Pritchett, J., et al. (2011). Understanding the role of SOX9 in acquired diseases: lessons from development. Trends in Molecular Medicine, 17(3), 166–174.

    PubMed  CAS  Google Scholar 

  71. Dorrell, C., et al. (2011). Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice. Genes & Development, 25(11), 1193–1203.

    CAS  Google Scholar 

  72. Scarpelli, D. G., & Rao, M. S. (1981). Differentiation of regenerating pancreatic cells into hepatocyte-like cells. Proceedings of the National Academy of Sciences of the United States of America, 78(4), 2577–2581.

    PubMed  CAS  Google Scholar 

  73. Rosenberg, L., Duguid, W. P., & Vinik, A. I. (1989). The effect of cellophane wrapping of the pancreas in the Syrian golden hamster: autoradiographic observations. Pancreas, 4(1), 31–37.

    PubMed  CAS  Google Scholar 

  74. Rosenberg, L. (1995). In vivo cell transformation: neogenesis of beta cells from pancreatic ductal cells. Cell Transplantation, 4(4), 371–383.

    PubMed  CAS  Google Scholar 

  75. Wang, R. N., Kloppel, G., & Bouwens, L. (1995). Duct- to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats. Diabetologia, 38(12), 1405–1411.

    PubMed  CAS  Google Scholar 

  76. Bonner-Weir, S., et al. (2000). In vitro cultivation of human islets from expanded ductal tissue. Proceedings of the National Academy of Sciences of the United States of America, 97(14), 7999–8004.

    PubMed  CAS  Google Scholar 

  77. Pour, P. M., Pandey, K. K., & Batra, S. K. (2003). What is the origin of pancreatic adenocarcinoma? Molecular Cancer, 2, 13.

    PubMed  Google Scholar 

  78. Solar, M., et al. (2009). Pancreatic exocrine duct cells give rise to insulin-producing beta cells during embryogenesis but not after birth. Developmental Cell, 17(6), 849–860.

    PubMed  CAS  Google Scholar 

  79. Zulewski, H., 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(3), 521–533.

    PubMed  CAS  Google Scholar 

  80. Hunziker, E., & Stein, M. (2000). Nestin-expressing cells in the pancreatic islets of Langerhans. Biochemical and Biophysical Research Communications, 271(1), 116–119.

    PubMed  CAS  Google Scholar 

  81. Selander, L., & Edlund, H. (2002). Nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas. Mechanisms of Development, 113(2), 189–192.

    PubMed  CAS  Google Scholar 

  82. Lardon, J., Rooman, I., & Bouwens, L. (2002). Nestin expression in pancreatic stellate cells and angiogenic endothelial cells. Histochemistry and Cell Biology, 117(6), 535–540.

    PubMed  CAS  Google Scholar 

  83. Dor, Y., et al. (2004). Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature, 429(6987), 41–46.

    PubMed  CAS  Google Scholar 

  84. Xu, X., et al. (2008). Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell, 132(2), 197–207.

    PubMed  CAS  Google Scholar 

  85. Tosh, D., Shen, C. N., & Slack, J. M. (2002). Differentiated properties of hepatocytes induced from pancreatic cells. Hepatology, 36(3), 534–543.

    PubMed  CAS  Google Scholar 

  86. Slack, J. M., & Tosh, D. (2001). Transdifferentiation and metaplasia–switching cell types. Current Opinion in Genetics and Development, 11(5), 581–586.

    PubMed  CAS  Google Scholar 

  87. Tosh, D., & Slack, J. M. (2002). How cells change their phenotype. Nature Reviews Molecular Cell Biology, 3(3), 187–194.

    PubMed  CAS  Google Scholar 

  88. Araki, M., & Okada, T. S. (1977). Differentiation of lens and pigment cells in cultures of neural retinal cells of early chick embryos. Developmental Biology, 60(1), 278–286.

    PubMed  CAS  Google Scholar 

  89. Bae, J. Y., et al. (2002). Intestinal type cholangiocarcinoma of intrahepatic large bile duct associated with hepatolithiasis–a new histologic subtype for further investigation. Hepato-Gastroenterology, 49(45), 628–630.

    PubMed  Google Scholar 

  90. Elmore, L. W., & Sirica, A. E. (1991). Phenotypic characterization of metaplastic intestinal glands and ductular hepatocytes in cholangiofibrotic lesions rapidly induced in the caudate liver lobe of rats treated with furan. Cancer Research, 51(20), 5752–5759.

    PubMed  CAS  Google Scholar 

  91. Elmore, L. W., & Sirica, A. E. (1993). “Intestinal-type” of adenocarcinoma preferentially induced in right/caudate liver lobes of rats treated with furan. Cancer Research, 53(2), 254–259.

    PubMed  CAS  Google Scholar 

  92. Krakowski, M. L., et al. (1999). Pancreatic expression of keratinocyte growth factor leads to differentiation of islet hepatocytes and proliferation of duct cells. American Journal of Pathology, 154(3), 683–691.

    PubMed  CAS  Google Scholar 

  93. Paner, G. P., Thompson, K. S., & Reyes, C. V. (2000). Hepatoid carcinoma of the pancreas. Cancer, 88(7), 1582–1589.

    PubMed  CAS  Google Scholar 

  94. Wolfe-Coote, S., et al. (1996). The non-human primate endocrine pancreas: development, regeneration potential and metaplasia. Cell Biology International, 20(2), 95–101.

    PubMed  CAS  Google Scholar 

  95. Longnecker, D. S., et al. (1979). Transplantation of azaserine-induced carcinomas of pancreas in rats. Cancer Letters, 7(4), 197–202.

    PubMed  CAS  Google Scholar 

  96. Christophe, J. (1994). Pancreatic tumoral cell line AR42J: an amphicrine model. American Journal of Physiology, 266(6 Pt 1), G963–G971.

    PubMed  CAS  Google Scholar 

  97. Mashima, H., et al. (1996). Betacellulin and activin A coordinately convert amylase-secreting pancreatic AR42J cells into insulin-secreting cells. The Journal of Clinical Investigation, 97(7), 1647–1654.

    PubMed  CAS  Google Scholar 

  98. Zhou, J., et al. (1999). Glucagon-like peptide 1 and exendin-4 convert pancreatic AR42J cells into glucagon- and insulin-producing cells. Diabetes, 48(12), 2358–2366.

    PubMed  CAS  Google Scholar 

  99. Shen, C. N., Slack, J. M., & Tosh, D. (2000). Molecular basis of transdifferentiation of pancreas to liver. Nature Cell Biology, 2(12), 879–887.

    PubMed  CAS  Google Scholar 

  100. Shen, C. N., et al. (2003). Glucocorticoids suppress beta-cell development and induce hepatic metaplasia in embryonic pancreas. Biochemical Journal, 375(Pt 1), 41–50.

    PubMed  CAS  Google Scholar 

  101. Marek, C. J., et al. (2003). Generation of hepatocytes expressing functional cytochromes P450 from a pancreatic progenitor cell line in vitro. Biochemical Journal, 370(Pt 3), 763–769.

    PubMed  CAS  Google Scholar 

  102. Kurash, J. K., Shen, C. N., & Tosh, D. (2004). Induction and regulation of acute phase proteins in transdifferentiated hepatocytes. Experimental Cell Research, 292(2), 342–358.

    PubMed  CAS  Google Scholar 

  103. Westmacott, A., et al. (2006). C/EBPalpha and C/EBPbeta are markers of early liver development. International Journal of Developmental Biology, 50(7), 653–657.

    PubMed  CAS  Google Scholar 

  104. Lee, B. C., Hendricks, J. D., & Bailey, G. S. (1989). Metaplastic pancreatic cells in liver tumors induced by diethylnitrosamine. Experimental and Molecular Pathology, 50(1), 104–113.

    PubMed  CAS  Google Scholar 

  105. Hendricks, J. D., Meyers, T. R., & Shelton, D. W. (1984). Histological progression of hepatic neoplasia in rainbow trout (Salmo gairdneri). National Cancer Institute Monograph, 65, 321–336.

    PubMed  CAS  Google Scholar 

  106. Dashwood, R. H., et al. (1989). In vivo disposition of the natural anti-carcinogen indole-3-carbinol after po administration to rainbow trout. Food and Chemical Toxicology, 27(6), 385–392.

    PubMed  CAS  Google Scholar 

  107. Horb, M. E., et al. (2003). Experimental conversion of liver to pancreas. Current Biology, 13(2), 105–115.

    PubMed  CAS  Google Scholar 

  108. Sumazaki, R., et al. (2004). Conversion of biliary system to pancreatic tissue in Hes1-deficient mice. Nature Genetics, 36(1), 83–87.

    PubMed  CAS  Google Scholar 

  109. Burke, Z. D., Shen, C. N., & Tosh, D. (2004). Bile ducts as a source of pancreatic beta cells. Bioessays, 26(9), 932–937.

    PubMed  Google Scholar 

  110. Jensen, J., et al. (2000). Control of endodermal endocrine development by Hes-1. Nature Genetics, 24(1), 36–44.

    PubMed  CAS  Google Scholar 

  111. Lee, J. C., et al. (2001). Regulation of the pancreatic pro-endocrine gene neurogenin3. Diabetes, 50(5), 928–936.

    PubMed  CAS  Google Scholar 

  112. Pujari, B. D., & Deodhare, S. G. (1979). Intrahepatic ectopic pancreas: (report of a case). Indian Journal of Medical Sciences, 33(6), 157–159.

    PubMed  CAS  Google Scholar 

  113. Gadrat, J., et al. (1965). Intra-hepatic aberrent pancreas Two cases diagnosed by needle biopsy controlled by laparoscopy in two cirrhotics. Archives des Maladies de l’Appareil Digestif et des Maladies de la Nutrition, 54(11), 1143–1148.

    PubMed  CAS  Google Scholar 

  114. Mobini, J., Krouse, T. B., & Cooper, D. R. (1974). Intrahepatic pancreatic heterotopia: review and report of a case presenting as an abdominal mass. American Journal of Digestive Diseases, 19(1), 64–70.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Regenerative Medicine Department of Biology & Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK

    Zoë D. Burke & David Tosh

Authors
  1. Zoë D. Burke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Tosh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zoë D. Burke or David Tosh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burke, Z.D., Tosh, D. Ontogenesis of Hepatic and Pancreatic Stem Cells. Stem Cell Rev and Rep 8, 586–596 (2012). https://doi.org/10.1007/s12015-012-9350-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-012-9350-2

Keywords

Search

Navigation