Skip to main content
Book cover

Stem Cells Heterogeneity in Different Organs pp 81–93Cite as

Heterogeneity of Stem Cells in the Thyroid

Part of the Advances in Experimental Medicine and Biology book series (AEMB,volume 1169)

Abstract

Identification of thyroid stem cells in the past few years has made important contributions to our understanding of the cellular and molecular mechanisms that induce tissue regeneration and repair. Embryonic stem (ES) cells and induced-pluripotent stem cells have been used to establish reliable protocols to obtain mature thyrocytes and functional follicles for the treatment of thyroid diseases in mice. In addition, the discovery of resident thyroid progenitor cells, along with other sources of stem cells, has defined in detail the mechanisms responsible for tissue repair upon moderate or severe organ injury.

In this chapter, we highlight in detail the current state of research on thyroid stem cells by focusing on (1) the description of the first experiments performed to obtain thyroid follicles from embryonic stem cells, (2) the identification of resident stem cells in the thyroid gland, and (3) the definition of the current translational in vivo and in vitro models used for thyroid tissue repair and regeneration.

Keywords

  • Thyroid regeneration
  • Organ repair
  • Thyroid resident stem cells
  • Solid cell nest (SCN)
  • Side population (SP)
  • Embryonic stem cells (ES cells)
  • TSH
  • Activin-A
  • Thyrospheres
  • Thyroid follicles
  • Parafollicular cells
  • Thyroglobulin (Tg)
  • Thyroperoxidase (TPO)
  • Oct4
  • Sca1

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-030-24108-7_5
  • Chapter length: 13 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   119.00
Price excludes VAT (USA)
  • ISBN: 978-3-030-24108-7
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   159.99
Price excludes VAT (USA)
Hardcover Book
USD   219.99
Price excludes VAT (USA)
Learn about institutional subscriptions
Fig. 5.1
Fig. 5.2
Fig. 5.3

References

  1. Puglisi MA, Giuliani L, Fierabracci A (2008) Identification and characterization of a novel expandable adult stem/progenitor cell population in the human exocrine pancreas. J Endocrinol Investig 31(6):563–572

    CrossRef  CAS  Google Scholar 

  2. Maiorana A, Fierabracci A, Cianfarani S (2009) Isolation and characterization of omental adipose progenitor cells in children: a potential tool to unravel the pathogenesis of metabolic syndrome. Horm Res 72(6):348–358

    CAS  PubMed  Google Scholar 

  3. Gritti A, Parati EA, Cova L, Frolichsthal P, Galli R, Wanke E et al (1996) Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor. J Neurosci 16(3):1091–1100

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  4. Alessandri G, Pagano S, Bez A, Benetti A, Pozzi S, Iannolo G et al (2004) Isolation and culture of human muscle-derived stem cells able to differentiate into myogenic and neurogenic cell lineages. Lancet Lond Engl 364(9448):1872–1883

    CrossRef  CAS  Google Scholar 

  5. Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F et al (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 95(9):911–921

    CrossRef  CAS  PubMed  Google Scholar 

  6. Burger PE, Gupta R, Xiong X, Ontiveros CS, Salm SN, Moscatelli D et al (2009) High aldehyde dehydrogenase activity: a novel functional marker of murine prostate stem/progenitor cells. Stem Cells Dayt Ohio 27(9):2220–2228

    CrossRef  CAS  Google Scholar 

  7. Hoshi N, Kusakabe T, Taylor BJ, Kimura S (2007) Side population cells in the mouse thyroid exhibit stem/progenitor cell-like characteristics. Endocrinology 148(9):4251–4258

    CrossRef  CAS  PubMed  Google Scholar 

  8. Thomas T, Nowka K, Lan L, Derwahl M (2006) Expression of endoderm stem cell markers: evidence for the presence of adult stem cells in human thyroid glands. Thyroid Off J Am Thyroid Assoc 16(6):537–544

    CrossRef  CAS  Google Scholar 

  9. Fierabracci A, Puglisi MA, Giuliani L, Mattarocci S, Gallinella-Muzi M (2008) Identification of an adult stem/progenitor cell-like population in the human thyroid. J Endocrinol 198(3):471–487

    CrossRef  CAS  PubMed  Google Scholar 

  10. Lin R-Y, Davies TF (2006) Derivation and characterization of thyrocyte-like cells from embryonic stem cells in vitro. Methods Mol Biol Clifton NJ 330:249–261

    CAS  Google Scholar 

  11. Ozaki T, Matsubara T, Seo D, Okamoto M, Nagashima K, Sasaki Y et al (2012) Thyroid regeneration: characterization of clear cells after partial thyroidectomy. Endocrinology 153(5):2514–2525

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  12. Okamoto M, Hayase S, Miyakoshi M, Murata T, Kimura S (2013) Stem cell antigen 1-positive mesenchymal cells are the origin of follicular cells during thyroid regeneration. PLoS One 8(11):e80801

    CrossRef  PubMed  PubMed Central  Google Scholar 

  13. Chen CY, Kimura H, Landek-Salgado MA, Hagedorn J, Kimura M, Suzuki K et al (2009) Regenerative potentials of the murine thyroid in experimental autoimmune thyroiditis: role of CD24. Endocrinology 150(1):492–499

    CrossRef  CAS  PubMed  Google Scholar 

  14. Takano T (2007) Fetal cell carcinogenesis of the thyroid: theory and practice. Semin Cancer Biol 17(3):233–240

    CrossRef  CAS  PubMed  Google Scholar 

  15. Mitsutake N, Iwao A, Nagai K, Namba H, Ohtsuru A, Saenko V et al (2007) Characterization of side population in thyroid cancer cell lines: cancer stem-like cells are enriched partly but not exclusively. Endocrinology 148(4):1797–1803

    CrossRef  CAS  PubMed  Google Scholar 

  16. Zito G, Richiusa P, Bommarito A, Carissimi E, Russo L, Coppola A et al (2008) In vitro identification and characterization of CD133(pos) cancer stem-like cells in anaplastic thyroid carcinoma cell lines. PLoS One 3(10):e3544

    CrossRef  PubMed  PubMed Central  Google Scholar 

  17. Kimura S (2014) Thyroid regeneration: how stem cells play a role? Front Endocrinol 5:55

    Google Scholar 

  18. Mauchamp J, Mirrione A, Alquier C, André F (1998) Follicle-like structure and polarized monolayer: role of the extracellular matrix on thyroid cell organization in primary culture. Biol Cell 90(5):369–380

    CrossRef  CAS  PubMed  Google Scholar 

  19. Hoyes AD, Kershaw DR (1985) Anatomy and development of the thyroid gland. Ear Nose Throat J 64(7):318–333

    CAS  PubMed  Google Scholar 

  20. Lazzaro D, Price M, de Felice M, Di Lauro R (1991) The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. Dev Camb Engl 113(4):1093–1104

    CAS  Google Scholar 

  21. Mansouri A, Chowdhury K, Gruss P (1998) Follicular cells of the thyroid gland require Pax8 gene function. Nat Genet 19(1):87–90

    CrossRef  CAS  PubMed  Google Scholar 

  22. Kimura S, Hara Y, Pineau T, Fernandez-Salguero P, Fox CH, Ward JM et al (1996) The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes Dev 10(1):60–69

    CrossRef  CAS  PubMed  Google Scholar 

  23. De Felice M, Ovitt C, Biffali E, Rodriguez-Mallon A, Arra C, Anastassiadis K et al (1998) A mouse model for hereditary thyroid dysgenesis and cleft palate. Nat Genet 19(4):395–398

    CrossRef  PubMed  Google Scholar 

  24. Martinez Barbera JP, Clements M, Thomas P, Rodriguez T, Meloy D, Kioussis D et al (2000) The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation. Dev Camb Engl 127(11):2433–2445

    CAS  Google Scholar 

  25. Kennedy M, Firpo M, Choi K, Wall C, Robertson S, Kabrun N et al (1997) A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 386(6624):488–493

    CrossRef  CAS  PubMed  Google Scholar 

  26. Keller G, Snodgrass HR (1999) Human embryonic stem cells: the future is now. Nat Med 5(2):151–152

    CrossRef  CAS  PubMed  Google Scholar 

  27. Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292(5520):1389–1394

    CrossRef  CAS  PubMed  Google Scholar 

  28. Boheler KR, Czyz J, Tweedie D, Yang H-T, Anisimov SV, Wobus AM (2002) Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ Res 91(3):189–201

    CrossRef  CAS  PubMed  Google Scholar 

  29. Nishimura F, Yoshikawa M, Kanda S, Nonaka M, Yokota H, Shiroi A et al (2003) Potential use of embryonic stem cells for the treatment of mouse parkinsonian models: improved behavior by transplantation of in vitro differentiated dopaminergic neurons from embryonic stem cells. Stem Cells Dayt Ohio 21(2):171–180

    CrossRef  Google Scholar 

  30. Shirahashi H, Wu J, Yamamoto N, Catana A, Wege H, Wager B et al (2004) Differentiation of human and mouse embryonic stem cells along a hepatocyte lineage. Cell Transplant 13(3):197–211

    CrossRef  PubMed  Google Scholar 

  31. Lin R-Y, Kubo A, Keller GM, Davies TF (2003) Committing embryonic stem cells to differentiate into thyrocyte-like cells in vitro. Endocrinology 144(6):2644–2649

    CrossRef  CAS  PubMed  Google Scholar 

  32. Arufe MC, Lu M, Lin R-Y (2009) Differentiation of murine embryonic stem cells to thyrocytes requires insulin and insulin-like growth factor-1. Biochem Biophys Res Commun 381(2):264–270

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  33. Marians RC, Ng L, Blair HC, Unger P, Graves PN, Davies TF (2002) Defining thyrotropin-dependent and -independent steps of thyroid hormone synthesis by using thyrotropin receptor-null mice. Proc Natl Acad Sci U S A 99(24):15776–15781

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ma R, Latif R, Davies TF (2009) Thyrotropin-independent induction of thyroid endoderm from embryonic stem cells by activin A. Endocrinology 150(4):1970–1975

    CrossRef  CAS  PubMed  Google Scholar 

  35. Antonica F, Kasprzyk DF, Opitz R, Iacovino M, Liao X-H, Dumitrescu AM et al (2012) Generation of functional thyroid from embryonic stem cells. Nature 491(7422):66–71

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kurmann AA, Serra M, Hawkins F, Rankin SA, Mori M, Astapova I et al (2015) Regeneration of thyroid function by transplantation of differentiated pluripotent stem cells. Cell Stem Cell 17(5):527–542

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  37. Coclet J, Foureau F, Ketelbant P, Galand P, Dumont JE (1989) Cell population kinetics in dog and human adult thyroid. Clin Endocrinol 31(6):655–665

    CrossRef  CAS  Google Scholar 

  38. Dumont JE, Lamy F, Roger P, Maenhaut C (1992) Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors. Physiol Rev 72(3):667–697

    CrossRef  CAS  PubMed  Google Scholar 

  39. Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183(4):1797–1806

    CrossRef  CAS  PubMed  Google Scholar 

  40. Thomas D, Friedman S, Lin R-Y (2008) Thyroid stem cells: lessons from normal development and thyroid cancer. Endocr Relat Cancer 15(1):51–58

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF et al (1999) Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401(6751):390–394

    CAS  PubMed  Google Scholar 

  42. Hussain SZ, Strom SC, Kirby MR, Burns S, Langemeijer S, Ueda T et al (2005) Side population cells derived from adult human liver generate hepatocyte-like cells in vitro. Dig Dis Sci 50(10):1755–1763

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lan L, Cui D, Nowka K, Derwahl M (2007) Stem cells derived from goiters in adults form spheres in response to intense growth stimulation and require thyrotropin for differentiation into thyrocytes. J Clin Endocrinol Metab 92(9):3681–3688

    CrossRef  CAS  PubMed  Google Scholar 

  44. Goss RJ (1980) Animal models for growth. Proc Nutr Soc 39(3):213–217

    CrossRef  CAS  PubMed  Google Scholar 

  45. Bucher NL (1967) Experimental aspects of hepatic regeneration. N Engl J Med 277(14):738–746

    CrossRef  CAS  PubMed  Google Scholar 

  46. Clark OH, Lambert WR, Cavalieri RR, Rapoport B, Hammond ME, Ingbar SH (1976) Compensatory thyroid hypertrophy after hemithyroidectomy in rats. Endocrinology 99(4):988–995

    CrossRef  CAS  PubMed  Google Scholar 

  47. Johansen R, Gardner RE, Galante M, Marchi FF, Ledwich TW, Soley MH et al (1951) An experimental study of thyroid regeneration following subtotal thyroidectomy. Surg Gynecol Obstet 93(3):303–309

    CAS  PubMed  Google Scholar 

  48. Ahmed MT, Sinha AK, Pickard MR, Kim KD, Ekins RP (1993) Hypothyroidism in the adult rat causes brain region-specific biochemical dysfunction. J Endocrinol 138(2):299–305

    CrossRef  CAS  PubMed  Google Scholar 

  49. Biondo-Simões Mde LP, GRA C, Montibeller GR, Sadowski JA, Biondo-Simões R (2007) The influence of hypothyroidism on liver regeneration: an experimental study in rats. Acta Cir Bras 22(Suppl 1):52–56

    CrossRef  PubMed  Google Scholar 

  50. Chen B-Y, Wang X, Chen L-W, Luo Z-J (2012) Molecular targeting regulation of proliferation and differentiation of the bone marrow-derived mesenchymal stem cells or mesenchymal stromal cells. Curr Drug Targets 13(4):561–571

    CrossRef  CAS  PubMed  Google Scholar 

  51. Fong ELS, Chan CK, Goodman SB (2011) Stem cell homing in musculoskeletal injury. Biomaterials 32(2):395–409

    CrossRef  CAS  PubMed  Google Scholar 

  52. Mikhailov VM, Sokolova AV, Serikov VB, Kaminskaya EM, Churilov LP, Trunin EM et al (2012) Bone marrow stem cells repopulate thyroid in X-ray regeneration in mice. Pathophysiol Off J Int Soc Pathophysiol 19(1):5–11

    CAS  Google Scholar 

  53. Wollman SH, Hilfer SR (1978) Embryologic origin of the various epithelial cell types in the second kind of thyroid follicle in the C3H mouse. Anat Rec 191(1):111–121

    CrossRef  CAS  PubMed  Google Scholar 

  54. Burstein DE, Nagi C, Wang BY, Unger P (2004 Apr) Immunohistochemical detection of p53 homolog p63 in solid cell nests, papillary thyroid carcinoma, and Hashimoto’s thyroiditis: a stem cell hypothesis of papillary carcinoma oncogenesis. Hum Pathol 35(4):465–473

    CrossRef  CAS  PubMed  Google Scholar 

  55. Preto A, Cameselle-Teijeiro J, Moldes-Boullosa J, Soares P, Cameselle-Teijeiro JF, Silva P et al (2004) Telomerase expression and proliferative activity suggest a stem cell role for thyroid solid cell nests. Mod Pathol Off J U S Can Acad Pathol Inc. 17(7):819–826

    CAS  Google Scholar 

  56. Reis-Filho JS, Preto A, Soares P, Ricardo S, Cameselle-Teijeiro J, Sobrinho-Simões M (2003) p63 expression in solid cell nests of the thyroid: further evidence for a stem cell origin. Mod Pathol Off J U S Can Acad Pathol Inc 16(1):43–48

    Google Scholar 

  57. Ozaki T, Nagashima K, Kusakabe T, Kakudo K, Kimura S (2011) Development of thyroid gland and ultimobranchial body cyst is independent of p63. Lab Investig J Tech Methods Pathol 91(1):138–146

    CrossRef  CAS  Google Scholar 

  58. Drosos I, Kolios G (2013) Stem cells in liver regeneration and their potential clinical applications. Stem Cell Rev 9(5):668–684

    CrossRef  CAS  Google Scholar 

  59. Duncan AW, Dorrell C, Grompe M (2009) Stem cells and liver regeneration. Gastroenterology 137(2):466–481

    CrossRef  PubMed  Google Scholar 

  60. Gilgenkrantz H, Collin de l’Hortet A (2011) New insights into liver regeneration. Clin Res Hepatol Gastroenterol 35(10):623–629

    CrossRef  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biomedical Department of Internal and Specialist Medicine (DI.BI.MIS), Laboratory of Regenerative Medicine, Section of Endocrinology, Diabetology and Metabolism, University of Palermo, Palermo, Italy

    Giovanni Zito, Antonina Coppola, Giuseppe Pizzolanti & Carla Giordano

  2. Advanced Technologies Network (ATeN) Center, Laboratory of Stem Cells and Cellular Cultures, University of Palermo, Palermo, Italy

    Giovanni Zito, Antonina Coppola, Giuseppe Pizzolanti & Carla Giordano

Authors
  1. Giovanni Zito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonina Coppola
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giuseppe Pizzolanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carla Giordano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carla Giordano .

Editor information

Editors and Affiliations

  1. Department of Pathology, Federal University of Minas Gerais, Department of Radiology, Columbia University Medical Center, New York, NY, USA, Belo Horizonte, Minas Gerais, Brazil

    Dr. Alexander Birbrair

Rights and permissions

Reprints and Permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Verify currency and authenticity via CrossMark

Cite this chapter

Zito, G., Coppola, A., Pizzolanti, G., Giordano, C. (2019). Heterogeneity of Stem Cells in the Thyroid. In: Birbrair, A. (eds) Stem Cells Heterogeneity in Different Organs. Advances in Experimental Medicine and Biology, vol 1169. Springer, Cham. https://doi.org/10.1007/978-3-030-24108-7_5

Download citation