Skip to main content

Transcription Factor-Directed Differentiation of Stem Cells Along an Endocrine Lineage

  • Chapter
Stem Cells in Endocrinology

Part of the book series: Contemporary Endocrinology ((COE))

  • 485 Accesses

Abstract

Loss of endocrine gland function from a variety of causes (e.g., autoimmune destruction, infection, injury) is commonly encountered in clinical endocrinology. Although hormone replacement is generally adequate to replace the basic function of the gland and maintain viability, it typically cannot reproduce the intricate regulation of hormone secretion. Thus, despite the availability of hormone replacement, those who require it are often at risk for the development of long-term problems (e.g., microvascular complications or severe hypoglycemia in diabetes, complications of long-term overreplacement of hydrocortisone or inadequate hydrocortisone replacement during times of stress). Thus cell replacement therapy capable of restoring endocrine function similar to that of the native gland would represent a major therapeutic advance. To that end, the differentiation of stem cells to generate new endocrine cells offers great potential.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kyba M, Daley GQ. Hematopoiesis from embryonic stem cells: lessons from and for ontogeny. Exp Hematol 2003;31:994–1006.

    PubMed  CAS  Google Scholar 

  2. Payne KJ, Crooks GM. Human hematopoietic lineage commitment. Immunol Rev 2002;187:48–64.

    Article  PubMed  Google Scholar 

  3. Kyba M, Perlingeiro RC, Hoover RR, Lu CW, Pierce J, Daley GQ. Enhanced hematopoietic differentiation of embryonic stem cells conditionally expressing Stat5. Proc Natl Acad Sci USA 2003;100(Suppl. 1): 11904–11910.

    Article  PubMed  CAS  Google Scholar 

  4. Ihle JN. The Stat family in cytokine signaling. Curr Opin Cell Biol 2001;13:211–117.

    Article  PubMed  CAS  Google Scholar 

  5. Shuai K, Halpern J, ten Hoeve J, Rao X, Sawyers CL. Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia. Oncogene 1996;13:247–254.

    PubMed  CAS  Google Scholar 

  6. Kyba M, Perlingeiro RC, Daley GQ. HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Cell 2002;109:29–37.

    Article  PubMed  CAS  Google Scholar 

  7. Lee JE. Basic helix-loop-helix genes in neural development. Curr Opin Neurobiol 1997;7:13–20.

    Article  PubMed  Google Scholar 

  8. O’Shea KS. Neuronal differentiation of mouse embryonic stem cells: lineage selection and forced differentiation paradigms. Blood Cells Mol Dis 2001;27:705–712.

    Article  PubMed  CAS  Google Scholar 

  9. Wilson M, Koopman P. Matching SOX: partner proteins and co-factors of the SOX family of transcriptional regulators. Curr Opin Genet Dev 2002;12:441–446.

    Article  PubMed  CAS  Google Scholar 

  10. Pevny LH, Sockanathan S, Placzek M, Lovell-Badge R. A role for SOX1 in neural determination. Development 1998;125:1967–1978.

    PubMed  CAS  Google Scholar 

  11. Lee SH, Lumelsky N, Studer L, Auerbach JM, McKay RD. Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotechnol 2000;18:675–679.

    Article  PubMed  CAS  Google Scholar 

  12. Kim JH, Auerbach JM, Rodriguez-Gomez JA, et al. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 2002;418:50–56.

    Article  PubMed  CAS  Google Scholar 

  13. Ang SL, Wierda A, Wong D, et al. The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development 1993;119:1301–1315.

    PubMed  CAS  Google Scholar 

  14. Chakrabarti SK, Mirmira RG. Transcription factors direct the development and function of pancreatic beta cells. Trends Endocrinol Metab 2003;14:78–84.

    Article  PubMed  CAS  Google Scholar 

  15. Levinson-Dushnik M, Benvenisty N. Involvement of hepatocyte nuclear factor 3 in endoderm differentiation of embryonic stem cells. Mol Cell Biol 1997;17:3817–3822.

    PubMed  CAS  Google Scholar 

  16. Ang SL, Rossant J. HNF-3 beta is essential for node and notochord formation in mouse development. Cell 1994;78:561–574.

    Article  PubMed  CAS  Google Scholar 

  17. Weinstein DC, Ruiz i Altaba A, Chen WS, et al. The winged-helix transcription factor HNF-3 beta is required for notochord development in the mouse embryo. 1994;Cell 78:575–588.

    Article  PubMed  CAS  Google Scholar 

  18. Kemp DM, Thomas MK, Habener JF. Developmental aspects of the endocrine pancreas. Rev Endocr Metab Disord 2003;4:5–17.

    Article  PubMed  CAS  Google Scholar 

  19. Murtaugh LC, Melton DA. Genes, signals, and lineages in pancreas development. Annu Rev Cell Dev Biol 2003;19:71–89.

    Article  PubMed  CAS  Google Scholar 

  20. Jensen J. Gene regulatory factors in pancreatic development. Dev Dyn 2004;229:176–200.

    Article  PubMed  CAS  Google Scholar 

  21. Gradwohl G, Dierich A, LeMeur M, Guillemot F. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci USA 2000;97:1607–1611.

    Article  PubMed  CAS  Google Scholar 

  22. Schwitzgebel VM, Scheel DW, Conners JR, et al. Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development 2000;127:3533–3542.

    PubMed  CAS  Google Scholar 

  23. Soria B, Roche E, Berna G, Leon-Quinto T, Reig JA, Martin F. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 2000;49:157–162.

    Article  PubMed  CAS  Google Scholar 

  24. Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 2001;292:1389–1394.

    Article  PubMed  CAS  Google Scholar 

  25. Hori Y, Rulifson IC, Tsai BC, Heit JJ, Cahoy JD, Kim SK. Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc Natl Acad Sci USA 2002;99:16105–16110.

    Article  PubMed  CAS  Google Scholar 

  26. Blyszczuk P, Czyz J, Kania G, et al. Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Proc Natl Acad Sci USA 2003;100:998–1003.

    Article  PubMed  CAS  Google Scholar 

  27. Smith SB, Ee HC, Conners JR, German MS. Paired-homeodomain transcription factor PAX4 acts as a transcriptional repressor in early pancreatic development. Mol Cell Biol 1999;19: 8272–8280.

    PubMed  CAS  Google Scholar 

  28. Quaroni A, May RJ. Establishment and characterization of intestinal epithelial cell cultures. Meth Cell Biol 1980;21B:403–427.

    Article  Google Scholar 

  29. Yamada S, Kojima H, Fujimiya M, Nakamura T, Kashiwagi A, Kikkawa R. Differentiation of immature enterocytes into enteroendocrine cells by Pdx1 overexpression. Am J Physiol Gastrointest Liver Physiol 2001;281: G229–G236.

    PubMed  CAS  Google Scholar 

  30. Kojima H, Nakamura T, Fujita Y, et al. Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin. Diabetes 2002;51:1398–1408.

    Article  PubMed  CAS  Google Scholar 

  31. Yoshida S, Kajimoto Y, Yasuda T, et al. PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. Diabetes 2002;51:2505–2513.

    Article  PubMed  CAS  Google Scholar 

  32. Dunbar AJ, Goddard C. Structure-function and biological role of betacellulin. Int J Biochem Cell Biol 2000;32:805–815.

    Article  PubMed  CAS  Google Scholar 

  33. Huotari MA, Miettinen PJ, Palgi J, et al. ErbB signaling regulates lineage determination of developing pancreatic islet cells in embryonic organ culture. Endocrinology 2002;143:4437–4446.

    Article  PubMed  CAS  Google Scholar 

  34. Li L, Seno M, Yamada H, Kojima I. Promotion of beta-cell regeneration by betacellulin in ninety percent-pancreatectomized rats. Endocrinology 2001;142:5379–5385.

    Article  PubMed  CAS  Google Scholar 

  35. Demeterco C, Beattie GM, Dib SA, Lopez AD, Hayek A. A role for activin A and betacellulin in human fetal pancreatic cell differentiation and growth. J Clin Endocrinol Metab 2000;85:3892–3897.

    Article  PubMed  CAS  Google Scholar 

  36. Ahlgren U, Pfaff SL, Jessell TM, Edlund T, Edlund H. Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature 1997;385:257–260.

    Article  PubMed  CAS  Google Scholar 

  37. Meivar-Levy I, Ferber S. New organs from our own tissues: liver-to-pancreas transdifferentiation. Trends Endocrinol Metab 2003;14:460–466.

    Article  PubMed  CAS  Google Scholar 

  38. Grompe M. Pancreatic-hepatic switches in vivo. Mech Dev 2003;120:99–106.

    Article  PubMed  CAS  Google Scholar 

  39. Ferber S, Halkin A, Cohen H, et al. Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 2000;6:568–572.

    Article  PubMed  CAS  Google Scholar 

  40. Ber I, Shternhall K, Perl S, et al. Functional, persistent, and extended liver to pancreas transdifferentiation. J Biol Chem 2003;278:31950–1957.

    Article  PubMed  CAS  Google Scholar 

  41. Zalzman M, Gupta S, Giri RK, et al. Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells. Proc Natl Acad Sci USA 2003;100: 7253–7258.

    Article  PubMed  CAS  Google Scholar 

  42. Malhi H, Irani AN, Gagandeep S, Gupta S. Isolation of human progenitor liver epithelial cells with extensive replication capacity and differentiation into mature hepatocytes. J Cell Sci 2002;115:2679–2688.

    PubMed  CAS  Google Scholar 

  43. Petersen BE. Hepatic “stem” cells: coming full circle. Blood Cells Mol Dis 2001;27: 590–600.

    Article  PubMed  CAS  Google Scholar 

  44. Chan L, Fujimiya M, Kojima H. In vivo gene therapy for diabetes mellitus. Trends Mol Med 2003;9: 430–435.

    Article  PubMed  CAS  Google Scholar 

  45. Kojima H, Fujimiya M, Matsumura K, et al. NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat Med 2003;9:596–603.

    Article  PubMed  CAS  Google Scholar 

  46. Crawford PA, Sadovsky Y, Milbrandt J. Nuclear receptor steroidogenic factor 1 directs embryonic stem cells toward the steroidogenic lineage. Mol Cell Biol 1997;17:3997–4006.

    PubMed  CAS  Google Scholar 

  47. Parker KL, Rice DA, Lala DS, et al. Steroidogenic factor 1: an essential mediator of endocrine development. Recent Prog Horm Res 2002;57:19–36.

    Article  PubMed  CAS  Google Scholar 

  48. Sadovsky Y, Crawford PA, Woodson KG, et al. Mice deficient in the orphan receptor steroidogenic factor 1 lack adrenal glands and gonads but express P450 side-chain-cleavage enzyme in the placenta and have normal embryonic serum levels of corticosteroids. Proc Natl Acad Sci USA 1995;92:10939–10943.

    Article  PubMed  CAS  Google Scholar 

  49. Luo X, Ikeda Y, Parker KL. A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 1994;77:481–490.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Lowe, W.L. (2005). Transcription Factor-Directed Differentiation of Stem Cells Along an Endocrine Lineage. In: Lester, L.B. (eds) Stem Cells in Endocrinology. Contemporary Endocrinology. Humana Press. https://doi.org/10.1385/1-59259-900-1:133

Download citation

  • DOI: https://doi.org/10.1385/1-59259-900-1:133

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-407-4

  • Online ISBN: 978-1-59259-900-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics