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Age-related expressions of p63 and other keratinocyte stem cell markers in rat cornea

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

In this study, we examined the postnatal expression patterns of p63 and other keratinocyte stem cell markers in the rat cornea in an attempt to determine the markers that best represent characteristics of corneal keratinocyte stem cells. We show that the expression of p63 in the rat cornea is unique and differs from that observed in humans. It changes with age, from central cornea-positive, peripheral cornea-positive, and limbus-positive, to central cornea-positive, peripheral cornea-positive, and limbus-negative, and finally to central cornea-negative, peripheral cornea-positive, and limbus-negative, as examined by immunohistochemical staining. However, when a more sensitive staining method was used, the limbus was also shown to be positive for p63, indicating a lower level of expression than that of the peripheral cornea. The basal layer of the rat limbal epithelium is the site where β-catenin+, K14+, PCNA-, and K3- cells reside. This cell layer is also the site where slow-cycling cells are located. In contrast with observations made in humans, our results clearly indicate that p63 is expressed in stem cells and young transient amplifying cells of the rat cornea, with higher levels of expression in the latter.

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References

  1. Barnard Z, Apel AJ, Harkin DG. Phenotypic analyses of limbal epithelial cell cultures derived from donor corneoscleral rims. Clin Exp Ophthalmol 29:138–142;2001.

    Google Scholar 

  2. Barrandon Y, Green H. Three clonal types of keratinocyte with different capacities for multiplication. Proc Natl Acad Sci USA 84:2302–2306;1987.

    Google Scholar 

  3. Cotsarelis G, Cheng SZ, Dong G, Sun TT, Lavker RM. Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: Implications on epithelial stem cells. Cell 57:201–209;1989.

    Google Scholar 

  4. Cotsarelis G, Sun TT, Lavker RM. Label-retaining cells reside in the bulge area of pilosebaceous unit: Implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61:1329–1337;1990.

    Google Scholar 

  5. Coulombe PA, Kopan R, Fuchs E. Expression of keratin K14 in the epidermis and hair follicle: Insights into complex programs of differentiation. J Cell Biol 109:2295–2312;1989.

    Google Scholar 

  6. Davanger M, Evensen A. Role of the pericorneal papillary structure in renewal of corneal epithelium. Nature 229:560–561;1971.

    Google Scholar 

  7. Duplan JF, Monnot P. Radiosensitivity of mouse fetal liver stem cells during multiplication. Int J Radiat Biol Relat Stud Phys Chem Med 17:297–301;1970.

    Google Scholar 

  8. Dutting D, Gierer A, Hansmann G. Self-renewal of stem cells and differentiation of nerve cells in the developing chick retina. Brain Res 312:21–32;1983.

    Google Scholar 

  9. Ebato B, Friend J, Thoft RA. Comparison of limbal and peripheral human corneal epithelium in tissue culture. Invest Ophthalmol Vis Sci 29:1533–1537;1988.

    Google Scholar 

  10. Fradette J, Germain L, Seshaiah P, Coulombe PA. The type I keratin 19 possesses distinct and context-dependent assembly properties. J Biol Chem 273:35176–35184;1998.

    Google Scholar 

  11. Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3:393–403;1970.

    Google Scholar 

  12. Friedenstein AJ, Piatetzky S 2nd, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16:381–390;1966.

    Google Scholar 

  13. Fuchs E, Segre JA. Stem cells: A new lease on life. Cell 100:143–155;2000.

    Google Scholar 

  14. Gage F, Coates P, Palmer T, Kuhn H, Fisher L, Suhonen J, Peterson D, Suhr S, Ray J. Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc Natl Acad Sci USA 92:11879–11883;1995.

    Google Scholar 

  15. Gumbiner BM. Carcinogenesis: A balance between beta-catenin and APC. Curr Biol 7:443–446;1997.

    Google Scholar 

  16. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW. Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512;1998.

    Google Scholar 

  17. Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. Beta-catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105:533–545;2001.

    Google Scholar 

  18. Lajtha LG. Stem cell concepts. Differentiation 14:23–34;1979.

    Google Scholar 

  19. Lavker RM, Dong G, Cheng SZ, Kudoh K, Cotsarelis G, Sun TT. Relative proliferative rates of limbal and corneal epithelia. Implications of corneal epithelial migration, circadian rhythm, and suprabasally located DNA-synthesizing keratinocytes. Invest Ophthalmol Vis Sci 32:1864–1875;1991.

    Google Scholar 

  20. Lavker RM, Sun TT. Epidermal stem cells: Properties, markers, and location. Proc Natl Acad Sci USA 97:13473–13475;2000.

    Google Scholar 

  21. Leblond CP. The life history of cells in renewing systems. Am J Anat 160:114–158;1981.

    Google Scholar 

  22. McKay R. Stem cells in the central nervous system. Science 276:66–71;1997.

    Google Scholar 

  23. Michel M, Torok N, Godbout MJ, Lussier M, Gaudreau P, Royal A, Germain L. Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: Keratin 19 expressing cells are differentially localized in function of anatomic sites, and their number varies with donor age and culture stage. J Cell Sci 109:1017–1028;1996.

    Google Scholar 

  24. Millar SJ, Lavker RM, Sun TT. Keratinocyte stem cells of cornea, skin and hair follicle: Common and distinguishing features. Dev Biol 4:217–240;1993.

    Google Scholar 

  25. Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24;1982.

    Google Scholar 

  26. Moore JF, McMullen CF, Mahon GF, Adamis AP. The corneal epithelial stem cell. DNA Cell Biol 21:443–451;2002.

    Google Scholar 

  27. Morrison SJ, Shah NM, Anderson DJ. Regulatory mechanisms in stem cell biology. Cell 88:287–298;1997.

    Google Scholar 

  28. Nusse R. WNT targets. Repression and activation. Trends Genet 15:1–3;1999.

    Google Scholar 

  29. O'Guin WM, Galvin S, Schermer A, Sun TT. Patterns of keratin expression define distinct pathways of epithelial development and differentiation. Curr Top Dev Biol 22:97–125;1987.

    Google Scholar 

  30. Owen M. Marrow stromal stem cells. J Cell Sci Suppl 10:63–76;1988.

    Google Scholar 

  31. Pellegrini G, Dellambra E, Golisano O, Martinelli E, Fantozzi I, Bondanza S, Ponzin D, McKeon F, De Luca M. p63 identifies keratinocyte stem cells. Proc Natl Acad Sci USA 98:3156–3161;2001.

    Google Scholar 

  32. Pellegrini G, Golisano O, Paterna P, Lambiase A, Bonini S, Rama P, De Luca M. Location and clonal analysis of stem cells and their differentiated progeny in the human ocular surface. J Cell Biol 145:769–782;1999.

    Google Scholar 

  33. Potten CS, Morris RJ. Epithelial stem cells in vivo. J Cell Sci Suppl 10:45–62;1988.

    Google Scholar 

  34. Reichenbach A. Two types of neuronal precursor cells in the mammalian retina — A short review. J Hirnforsch 34:335–341;1993.

    Google Scholar 

  35. Reichenbach A, Schnitzer J, Friedrich A, Ziegert W, Bruckner G, Schober W. Development of the rabbit retina. I. Size of eye and retina, and postnatal cell proliferation. Anat Embryol (Berl) 183:287–297;1991.

    Google Scholar 

  36. Rodrigues M, Ben-Zvi A, Krachmer J, Schermer A, Sun TT. Suprabasal expression of a 64-kilodalton keratin (no. 3) in developing human corneal epithelium. Differentiation 34:60–67;1987.

    Google Scholar 

  37. Schultz E. Fine structure of satellite cells in growing skeletal muscle. Am J Anat 147:49–70;1976.

    Google Scholar 

  38. Sun TT, Eichner R, Nelson WG, Tseng SC, Weiss RA, Jarvinen M, Woodcock-Mitchell J. Keratin classes: Molecular markers for different types of epithelial differentiation. J Invest Dermatol 81:109–115s;1983.

    Google Scholar 

  39. Sun TT, Eichner R, Nelson WG, Vidrich A, Woodcock-Mitchell J. Keratin expression during normal epidermal differentiation. Curr Probl Dermatol 11:277–291;1983.

    Google Scholar 

  40. Taylor RB. Pluripotential stem cells in mouse embryo liver. Br J Exp Pathol 46:376–383;1965.

    Google Scholar 

  41. Tetsu O, McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426;1999.

    Google Scholar 

  42. Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C, McKeon F. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398:714–718;1999.

    Google Scholar 

  43. Zhu AJ, Watt FM. Beta-catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion. Development 126:2285–2298;1999.

    Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, College of Medicine, Chang Gung University, 259 Wenhua 1st Road Kweishan, 333, Taoyuan, Taiwan

    Yi-Jen Hsueh, Der-Yuan Wang, Chien-Chia Cheng &  Jan-Kan Chen

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  1. Yi-Jen Hsueh
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Hsueh, YJ., Wang, DY., Cheng, CC. et al. Age-related expressions of p63 and other keratinocyte stem cell markers in rat cornea. J Biomed Sci 11, 641–651 (2004). https://doi.org/10.1007/BF02256130

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  • DOI: https://doi.org/10.1007/BF02256130

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