Skip to main content
SpringerLink
Log in

Re-Assessing K15 as an Epidermal Stem Cell Marker

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

Abstract

The intermediate filament keratin 15 (K15) is present in variable amounts in various stratified epithelia, but has also been reported to be a stem cell marker in the hair follicle. Using peptide specific antibodies, we evaluated the temporal and spatial distribution pattern of K15 expression/localization during normal epidermal development and initiation of hair follicle formation, and in the injured mature epidermis (e.g., during acute injury and repair and in tumorigenesis). During development, K15 expression is first localized to a subset of epidermal basal cells and the overlying periderm at E12.5, but its expression is seen throughout the basal layer by E15.5 and beyond. In hair follicle morphogenesis, initial peg formation occurs in a K15-null area at E14.5 and as peg elongation proceeds through to the mature hair follicle, K15 expression follows the leading edge with positive cells restricted to the outer root sheath. In an epidermal injury model, K15 is first up-regulated and associated with both the basal and suprabasal layers of the interfollicular epidermis then expression becomes sporadic and down-regulated before a basal layer-specific association is re-established in the repaired epidermis. During tumorigenesis, K15 is first mis-expressed, and is ultimately down-regulated. Our data suggest that K15 protein expression may reflect not only expression in a stem or progenitor cell subpopulation, but also reflects the activity and responsiveness of basal-like cells to loss of homeostasis of the epidermal differentiation program. Thus, the data suggest caution in using K15 alone to delineate epidermal stem cells, and underscore the need for further investigation of K15 and other markers in epidermal cell subpopulations.

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
Fig. 3
Fig. 4

References

  1. Oriolo, A. S., Wald, F. A., Ramsauer, V. P., & Salas, P. J. (2007). Exp Cell Res, 313, 2255–2264.

    Article  PubMed  CAS  Google Scholar 

  2. Gu, L. H., & Coulombe, P. A. (2007). Curr Opin Cell Biol, 19, 13–23.

    Article  PubMed  CAS  Google Scholar 

  3. Magin, T. M., Vijayaraj, P., & Leube, R. E. (2007). Exp Cell Res, 313, 2021–2032.

    Article  PubMed  CAS  Google Scholar 

  4. Moll, R., Divo, M., & Langbein, L. (2008). Histochem Cell Biol, 129, 705–733.

    Article  PubMed  CAS  Google Scholar 

  5. Blanpain, C., & Fuchs, E. (2006). Annu Rev Cell Dev Biol, 22, 339–373.

    Article  PubMed  CAS  Google Scholar 

  6. Schweizer, J., Bowden, P. E., Coulombe, P. A., Langbein, L., Lane, E. B., Magin, T. M., et al. (2006). J Cell Biol, 174, 169–174.

    Article  PubMed  CAS  Google Scholar 

  7. Fuchs, E. (1995). Annu Rev Cell Dev Biol, 11, 123–153.

    Article  PubMed  CAS  Google Scholar 

  8. Lloyd, C., Yu, Q. C., Cheng, J., Turksen, K., Degenstein, L., Hutton, E., et al. (1995). J Cell Biol, 129, 1329–1344.

    Article  PubMed  CAS  Google Scholar 

  9. Smedts, F., Ramaekers, F., Leube, R. E., Keijser, K., Link, M., & Vooijs, P. (1993). Am J Pathol, 142, 403–412.

    PubMed  CAS  Google Scholar 

  10. Waseem, A., Dogan, B., Tidman, N., Alam, Y., Purkis, P., Jackson, S., et al. (1999). J Invest Dermatol, 112, 362–369.

    Article  PubMed  CAS  Google Scholar 

  11. Whitbread, L. A., & Powell, B. C. (1998). Exp Cell Res, 244, 448–459.

    Article  PubMed  CAS  Google Scholar 

  12. Moll, R., Franke, W. W., Schiller, D. L., Geiger, B., & Krepler, R. (1982). Cell, 31, 11–24.

    Article  PubMed  CAS  Google Scholar 

  13. Coulombe, P. A., Kopan, R., & Fuchs, E. (1989). J Cell Biol, 109, 2295–2312.

    Article  PubMed  CAS  Google Scholar 

  14. Reichelt, J., Bussow, H., Grund, C., & Magin, T. M. (2001). Mol Biol Cell, 12, 1557–1568.

    PubMed  CAS  Google Scholar 

  15. Troy, T. C., & Turksen, K. (1999). J Cell Physiol, 180, 409–421.

    Article  PubMed  CAS  Google Scholar 

  16. Peters, B., Kirfel, J., Bussow, H., Vidal, M., & Magin, T. M. (2001). Mol Biol Cell, 12, 1775–1789.

    PubMed  CAS  Google Scholar 

  17. Cotsarelis, G. (2006). J Invest Dermatol, 126, 1459–1468.

    Article  PubMed  CAS  Google Scholar 

  18. Lyle, S., Christofidou-Solomidou, M., Liu, Y., Elder, D. E., Albelda, S., & Cotsarelis, G. (1998). J Cell Sci, 111(Pt 21), 3179–3188.

    PubMed  CAS  Google Scholar 

  19. Pontiggia, L., Biedermann, T., Meuli, M., Widmer, D., Bottcher-Haberzeth, S., Schiestl, C., et al. (2009). J Invest Dermatol, 129, 480–490.

    Article  PubMed  CAS  Google Scholar 

  20. Roh, C., Roche, M., Guo, Z., Photopoulos, C., Tao, Q., & Lyle, S. (2008). In Vitro Cell Dev Biol Anim, 44, 236–244.

    Article  PubMed  CAS  Google Scholar 

  21. Liu, Y., Lyle, S., Yang, Z., & Cotsarelis, G. (2003). J Invest Dermatol, 121, 963–968.

    Article  PubMed  CAS  Google Scholar 

  22. Turksen, K. (2004). Dev Cell, 6, 454–456.

    Article  PubMed  CAS  Google Scholar 

  23. Webb, A., Li, A., & Kaur, P. (2004). Differentiation, 72, 387–395.

    Article  PubMed  Google Scholar 

  24. Omoto, M., Miyashita, H., Shimmura, S., Higa, K., Kawakita, T., Yoshida, S., et al. (2009). Invest Ophthalmol Vis Sci, 50, 2109–2115.

    Article  PubMed  Google Scholar 

  25. Tiede, S., Koop, N., Kloepper, J. E., Fassler, R., & Paus, R. (2009). Stem Cells, 27, 2793–2803.

    Article  PubMed  CAS  Google Scholar 

  26. Turksen, K., & Troy, T. C. (2002). Development, 129, 1775–1784.

    PubMed  CAS  Google Scholar 

  27. Troy, T. C., Rahbar, R., Arabzadeh, A., Cheung, R. M., & Turksen, K. (2005). Mech Dev, 122, 805–819.

    Article  PubMed  CAS  Google Scholar 

  28. Arabzadeh, A., Troy, T. C., & Turksen, K. (2007). BMC Cancer, 7, 196.

    Article  PubMed  Google Scholar 

  29. Arabzadeh, A., Troy, T. C., & Turksen, K. (2008). J Invest Dermatol, 128, 237–240.

    Article  PubMed  CAS  Google Scholar 

  30. Leube, R. E., Bader, B. L., Bosch, F. X., Zimbelmann, R., Achtstaetter, T., & Franke, W. W. (1988). J Cell Biol, 106, 1249–1261.

    Article  PubMed  CAS  Google Scholar 

  31. Porter, R. M., Lunny, D. P., Ogden, P. H., Morley, S. M., McLean, W. H., Evans, A., et al. (2000). Lab Invest, 80, 1701–1710.

    Article  PubMed  CAS  Google Scholar 

  32. Squier, C. A. & Kremer, M. J. (2001). J Natl Cancer Inst Monogr, 7–15.

  33. Troy, T. C., Arabzadeh, A., Yerlikaya, S., & Turksen, K. (2007). Cell Tissue Res, 330, 381–388.

    Article  PubMed  CAS  Google Scholar 

  34. Rentrop, M., Knapp, B., Winter, H., & Schweizer, J. (1986). J Cell Biol, 103, 2583–2591.

    Article  PubMed  CAS  Google Scholar 

  35. Schweizer, J., Rentrop, M., Nischt, R., Kinjo, M., & Winter, H. (1988). Cell Tissue Res, 253, 221–229.

    Article  PubMed  CAS  Google Scholar 

  36. Larouche, D., Tong, X., Fradette, J., Coulombe, P. A., & Germain, L. (2008). FASEB J, 22, 1404–1415.

    Article  PubMed  CAS  Google Scholar 

  37. Byrne, C., Hardman, M., & Nield, K. (2003). J Anat, 202, 113–123.

    Article  PubMed  Google Scholar 

  38. Marshall, D., Hardman, M. J., & Byrne, C. (2000). J Invest Dermatol, 114, 967–975.

    Article  PubMed  CAS  Google Scholar 

  39. Troy, T. C., Li, Y., O'Malley, L., & Turksen, K. (2007). Gene Expr Patterns, 7, 423–430.

    Article  PubMed  CAS  Google Scholar 

  40. Mack, J. A., Anand, S., & Maytin, E. V. (2005). Birth Defects Res C Embryo Today, 75, 314–329.

    Article  PubMed  CAS  Google Scholar 

  41. Hardman, M. J., Sisi, P., Banbury, D. N., & Byrne, C. (1998). Development, 125, 1541–1552.

    PubMed  CAS  Google Scholar 

  42. Byrne, C., Tainsky, M., & Fuchs, E. (1994). Development, 120, 2369–2383.

    PubMed  CAS  Google Scholar 

  43. Lu, H., Hesse, M., Peters, B., & Magin, T. M. (2005). Eur J Cell Biol, 84, 709–718.

    Article  PubMed  CAS  Google Scholar 

  44. McGowan, K. M., & Coulombe, P. A. (1998). J Cell Biol, 143, 469–486.

    Article  PubMed  CAS  Google Scholar 

  45. Fuchs, E., & Byrne, C. (1994). Curr Opin Genet Dev, 4, 725–736.

    Article  PubMed  CAS  Google Scholar 

  46. Fuchs, E. (2007). Nature, 445, 834–842.

    Article  PubMed  CAS  Google Scholar 

  47. Blanpain, C., & Fuchs, E. (2009). Nat Rev Mol Cell Biol, 10, 207–217.

    Article  PubMed  CAS  Google Scholar 

  48. Elias, P. M., Ahn, S. K., Denda, M., Brown, B. E., Crumrine, D., Kimutai, L. K., et al. (2002). J Invest Dermatol, 119, 1128–1136.

    Article  PubMed  CAS  Google Scholar 

  49. Coulombe, P. A. (1997). Biochem Biophys Res Commun, 236, 231–238.

    Article  PubMed  CAS  Google Scholar 

  50. Paladini, R. D., Takahashi, K., Bravo, N. S., & Coulombe, P. A. (1996). J Cell Biol, 132, 381–397.

    Article  PubMed  CAS  Google Scholar 

  51. Mazzalupo, S., Wong, P., Martin, P., & Coulombe, P. A. (2003). Dev Dyn, 226, 356–365.

    Article  PubMed  CAS  Google Scholar 

  52. DePianto, D., & Coulombe, P. A. (2004). Exp Cell Res, 301, 68–76.

    Article  PubMed  CAS  Google Scholar 

  53. Werner, S., & Munz, B. (2000). Exp Cell Res, 254, 80–90.

    Article  PubMed  CAS  Google Scholar 

  54. DiGiovanni, J. (1992). Pharmacol Ther, 54, 63–128.

    Article  PubMed  CAS  Google Scholar 

  55. Hennings, H., Glick, A. B., Greenhalgh, D. A., Morgan, D. L., Strickland, J. E., Tennenbaum, T., et al. (1993). Proc Soc Exp Biol Med, 202, 1–8.

    PubMed  CAS  Google Scholar 

  56. Owens, D. M., Wei, S., & Smart, R. C. (1999). Carcinogenesis, 20, 1837–1844.

    Article  PubMed  CAS  Google Scholar 

  57. Toftgard, R., Yuspa, S. H., & Roop, D. R. (1985). Cancer Res, 45, 5845–5850.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Jane E. Aubin (University of Toronto) for her continued support of our work. We also acknowledge the hard work of Zaida J. Ticas (MLT) (University of Ottawa) who meticulously prepares our paraffin-embedded sections. KT expresses his deepest appreciation for Tammy Troy’s continuous loyalty, support and fantastic work over the years. In addition, he is delighted to see the joy that young Anthony has brought to her life. As Rick said “I think this is the beginning of a beautiful friendship”. Try not to think of this as an end of an era, but rather the beginning of a new one. This work was supported by a research grant from the Canadian Institutes of Health Research (MOP 84464).

Conflicts of interest

The authors declare no potential conflicts of interest.

Author information

Authors and Affiliations

  1. Regenerative Medicine Program, Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute, 501 Smyth Road-CCW5226, Ottawa, Ontario, K1Y 8L6, Canada

    Tammy-Claire Troy, Azadeh Arabzadeh & Kursad Turksen

  2. Department of Cellular and Molecular Medicine, Ottawa, Ontario, Canada, K1Y 8L6

    Azadeh Arabzadeh & Kursad Turksen

  3. Department of Medicine, Divisions of Dermatology and Endocrinology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada, K1H 8M5

    Kursad Turksen

Authors
  1. Tammy-Claire Troy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Azadeh Arabzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kursad Turksen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tammy-Claire Troy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Troy, TC., Arabzadeh, A. & Turksen, K. Re-Assessing K15 as an Epidermal Stem Cell Marker. Stem Cell Rev and Rep 7, 927–934 (2011). https://doi.org/10.1007/s12015-011-9243-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-011-9243-9

Keywords

Search

Navigation