Skip to main content

Advertisement

SpringerLink
Log in

Label Retaining Cells and Cutaneous Stem Cells

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

Abstract

This is a comprehensive review on label retaining cells (LRC) in epidermal development and homeostasis. The precise in vivo identification and location of epidermal stem cells is a crucial issue in cutaneous biology. We discuss here the following problems: (1) Identification and location of LRC in the interfollicular epithelium and hair follicle; (2) The proliferative potential of LRC and their role in cutaneous homeostasis (3); LRC phenomenon and the Immortal Strand Hypothesis, which suggests an alternative mechanism for retention of genetic information; (4) Significance of LRC studies for development of stem cell concept. Now, it seems evident that LRC are a frequent feature of stem cell niches and revealing highly dormant LRC may be used for identification of stem cell niches in different tissues. LRC were used for screening specific markers of epidermal stem cells. Within a given tissue stem cells have different proliferative characteristics. There are more frequently cycling stem cells which function primarily in homeostasis, while LRC form a reserve of dormant, may be ultimate, stem cells, which are set aside for regeneration of injury or unforeseen need. The authors suggest that LRC dormancy described in Mammalia has much in common with developmental quiescence found in some other animals. For example in C. elegans reproductive system, vulval precursor cells have developmentally programmed cell-cycle arrest in the first larval stage, and then undergo an extended period of quiescence before resuming proliferation. Another example of developmental quiescence is the diapause, a widespread phenomenon exhibited by animals ranging from nematodes to mammals, often occurring at genetically predetermined life history stage.

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

Similar content being viewed by others

References

  1. Leblond, C. P., Greulich, R. C., & Marques-Pereira, J. P. (1964). Relationship of cell formation and cell migration in the renewal of stratified squamous epithelia. In W. Montagna & R. E. Billingham (Eds.), Advances in biology of skin, 5 (pp. 39–67). New York: Pergamon Press.

    Google Scholar 

  2. Rowe, L., & Dixon, W. J. (1972). Clustering and control of mitotic activity in human epidermis. Journal of Investigative Dermatology, 58, 16–23.

    PubMed  CAS  Google Scholar 

  3. Potten, C. S. (1974). The epidermal proliferative unit: The possible role of the central basal cell. Cell and Tissue Kinetics, 7, 77–88.

    PubMed  CAS  Google Scholar 

  4. Bryder, D., Rossi, D. J., & Weissman, I. L. (2006). Hematopoietic stem cells: The paradigmatic tissue-specific stem cell. American Journal of Pathology, 169(2), 338–346.

    PubMed  CAS  Google Scholar 

  5. Orkin, S. H., & Zon, L. I. (2008). Hematopoiesis: An evolving paradigm for stem cell biology. Cell, 132(4), 631–644.

    PubMed  CAS  Google Scholar 

  6. Mackenzie, I. C. (1970). Relationship between mitosis and the ordered structure of the stratum corneum in mouse epidermis. Nature, 226(5246), 653–655.

    PubMed  CAS  Google Scholar 

  7. Mackenzie, I. C. (1997). Retroviral transduction of murine epidermal stem cells demonstrates clonal units of epidermal structure. Journal of Investigative Dermatology, 109(3), 377–383.

    PubMed  CAS  Google Scholar 

  8. Mackenzie, I. C., Zimmerman, K., & Peterson, L. (1981). The pattern of cellular organization of human epidermis. Journal of Investigative Dermatology, 76(6), 459–461.

    PubMed  CAS  Google Scholar 

  9. Ghazizadeh, S., & Taichman, L. B. (2001). Multiple classes of stem cells in cutaneous epithelium: A lineage analysis of adult mouse skin. The EMBO Journal, 20, 1215–1222.

    PubMed  CAS  Google Scholar 

  10. Bickenbach, J. R. (1981). Identification and behavior of label-retaining cells in oral mucosa and skin. Journal of Dental Research, 60, C1611–C1620.

    Google Scholar 

  11. Bickenbach, J. R., & Mackenzie, I. C. (1984). Identification and localization of label retaining cells in hamster epithelium. Journal of Investigative Dermatology, 82(6), 618–622.

    PubMed  CAS  Google Scholar 

  12. Barrandon, Y., & Green, H. (1987). Three clonal types of keratinocyte with different capacities for multiplication. Proceedings of the National Academy of Sciences of the United States of America, 84(8), 2302–2306.

    PubMed  CAS  Google Scholar 

  13. Kolodka, T. M., Garlick, J. A., & Taichman, L. B. (1998). Evidence for keratinocyte stem cells in vitro: Long term engraftment and persistence of transgene expression from retrovirus-transduced keratinocytes. Proceedings of the National Academy of Sciences of the United States of America, 95(8), 4356–4361.

    PubMed  CAS  Google Scholar 

  14. Claudinot, S., Nicolas, M., Oshima, H., Rochat, A., & Barrandon, Y. (2005). Long-term renewal of hair follicles from clonogenic multipotent stem cells. Proceedings of the National Academy of Sciences of the United States of America, 102(41), 14677–14682.

    PubMed  CAS  Google Scholar 

  15. Compton, C. C., Gill, J. M., Bradford, D. A., Regauer, S., Gallico, G. G., & O'Connor, N. E. (1989). Skin regenerated from cultured epithelial autografts on full-thickness burn wounds from 6 days to 5 years after grafting. A light, electron microscopic and immunochemical study. Laboratory Investigation, 60(5), 600–612.

    PubMed  CAS  Google Scholar 

  16. Oshima, H., Inoue, H., Matsuzaki, K., Tanabe, M., & Kumagai, N. (2002). Permanent restoration of human skin treated with cultured epithelium grafting. Wound healing by stem cell based tissue engineering. Human Cell, 15, 118–128.

    PubMed  Google Scholar 

  17. Tumbar, T., Guasch, G., Greco, V., et al. (2004). Defining the epithelial stem cell niche in skin. Science, 303(5656), 359–363.

    PubMed  CAS  Google Scholar 

  18. Packard, D. S., Jr., Skalko, R. G., & Menzies, R. A. (1974). Growth retardation and cell death in mouse embryos following exposure to the teratogen bromodeoxyuridine. Experimental and Molecular Pathology, 21(1), 351–362.

    PubMed  CAS  Google Scholar 

  19. Bickenbach, J. R., McCutecheon, J., & Mackenzie, I. C. (1986). Rate of loss of tritiated thymidine label in basal cells in mouse epithelial tissues. Cell and Tissue Kinetics, 19(3), 325–333.

    PubMed  CAS  Google Scholar 

  20. Potten, C. S., Saffhill, R., & Maibach, H. I. (1987). Measurement of the transit time for cells through the epidermis and stratum corneum of the mouse and guinea-pig. Cell and Tissue Kinetics, 20(5), 461–472.

    PubMed  CAS  Google Scholar 

  21. Bickenbach, J. R., & Chism, E. (1998). Selection and extended growth of murine epidermal stem cells in culture. Experimental Cell Research, 244, 184–195.

    PubMed  CAS  Google Scholar 

  22. Mackenzie, I. C., & Bickenbach, J. R. (1985). Label-retaining keratinocytes and Langerhans cells in mouse epithelia. Cell and Tissue Research, 242(3), 551–556.

    PubMed  CAS  Google Scholar 

  23. Cotsarelis, G., Sun, T. T., & Lavker, R. M. (1990). 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.

    PubMed  CAS  Google Scholar 

  24. Taylor, G., Lehrer, M. S., Jensen, P. J., Sun, T.-T., & Lavker, R. M. (2000). Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell, 102, 451–461.

    PubMed  CAS  Google Scholar 

  25. Braun, K. M., Niemann, C., Jensen, U. B., Sundberg, J. P., Silva-Vargas, V., & Watt, F. M. (2003). Manipulation of stem cell proliferation and lineage commitment: Visualisation of label-retaining cells in wholemounts of mouse epidermis. Development, 130(21), 5241–5255.

    PubMed  CAS  Google Scholar 

  26. Pavlovitch, J. H., Rizk-Rabin, M., Jaffray, P., Hoehn, H., & Poot, M. (1991). Characteristics of homogeneously small keratinocytes from newborn rat skin: Possible epidermal stem cells. American Journal of Physiology, 261, 964–972.

    Google Scholar 

  27. Staiano-Coico, L., Higgins, P. J., Darzynkiewicz, Z., et al. (1986). Human keratinocyte culture. Identification and staging of epidermal cell subpopulations. The Journal of Clinical Investigation, 77, 396–404.

    PubMed  CAS  Google Scholar 

  28. Lavker, R. M., & Sun, T.-T. (1982). Heterogeneity in epidermal basal keratinocytes: Morphological and functional correlations. Science, 215, 1239–1241.

    PubMed  CAS  Google Scholar 

  29. Lavker, R. M., & Sun, T.-T. (1983). Epidermal stem cells. Journal of Investigative Dermatology (Supplement), 81, 121S–127S.

    CAS  Google Scholar 

  30. Nakamura, M., & Tokura, Y. (2009). The localization of label retaining cells in eccrine glands. Journal of Investigative Dermatology, 129, 2077–2078.

    PubMed  CAS  Google Scholar 

  31. Jones, P. H., Harper, S., & Watt, F. M. (1995). Stem cell patterning and fate in human epidermis. Cell, 80, 83–93.

    PubMed  CAS  Google Scholar 

  32. Jones, P. H., & Watt, F. M. (1993). Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell, 73, 713–724.

    PubMed  CAS  Google Scholar 

  33. Pittelkow, M. R., Wille, J. J., & Scott, R. E. (1986). Two functionally distinct classes of growth arrest states in human prokeratinocytes that regulate clonogenic potential. Journal of Investigative Dermatology, 86, 410–417.

    PubMed  CAS  Google Scholar 

  34. Vorotelyak, E. A., Tsitrin, E. B., Vasiliev, A. V., & Terskikh, V. V. (2005). Cultured human keratinocytes retaining label for a long time. Doklady Biological Sciences, 402, 221–223.

    PubMed  CAS  Google Scholar 

  35. Morris, R. J., & Potten, C. S. (1994). Slowly cycling (label-retaining) epidermal cells behave like clonogenic stem cells in vitro. Cell Proliferation, 27, 279–289.

    PubMed  CAS  Google Scholar 

  36. Stenn, K. S., & Paus, R. (2001). Controls of hair follicle cycling. Physiological Reviews, 81, 449–494.

    PubMed  CAS  Google Scholar 

  37. Lavker, R. M., Cotsarelis, G., Wei, Z. G., & Sun, T.-T. (1991). Stem cells of pelage, vibrissae, and eyelash follicles: The hair cycle and tumor formation. Annals of the New York Academy of Sciences, 642, 214–225.

    PubMed  CAS  Google Scholar 

  38. Lavker, R. M., Miller, S., Wilson, C., et al. (1993). Hair follicle stem cells: Their location, role in hair cycle, and involvement in skin tumor formation. Journal of Investigative Dermatology, 101(1 Suppl), 16S–26S.

    PubMed  CAS  Google Scholar 

  39. Paus, R., Müller-Röver, S., van der Veen, C., et al. (1999). A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis. Journal of Investigative Dermatology, 113, 523–532.

    PubMed  CAS  Google Scholar 

  40. Sun, T.-T., Cotsarelis, G., & Lavker, R. M. (1991). Hair follicle stem cells: The bulge-activation hypothesis. Journal of Investigative Dermatology, 96(5), 77S–78S.

    PubMed  CAS  Google Scholar 

  41. Panteleyev, A. A., Jahoda, C. A. B., & Christiano, A. M. (2001). Hair follicle predetermination. Journal of Cell Science, 114, 3419–3431.

    PubMed  CAS  Google Scholar 

  42. Morris, R. J., & Potten, C. S. (1999). Highly persistent label-retaining cells in the hair follicles of mice and their fate following induction of anagen. Journal of Investigative Dermatology, 112, 470–475.

    PubMed  CAS  Google Scholar 

  43. Ito, M., Kizawa, K., Toyoda, M., & Morohashi, M. (2002). Label-retaining cells in the bulge region are directed to cell death after plucking, followed by healing from the surviving hair germ. Journal of Investigative Dermatology, 119, 1310–1316.

    PubMed  CAS  Google Scholar 

  44. Kobayashi, K., Rochat, A., & Barrandon, Y. (1993). Segregation of keratinocyte colony-forming cells in the bulge of the rat vibrissa. Proceedings of the National Academy of Sciences of the United States of America, 90, 7391–7395.

    PubMed  CAS  Google Scholar 

  45. Oshima, H., Rochat, A., Kedzia, C., Kobayashi, K., & Barrandon, Y. (2001). Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell, 104, 233–245.

    PubMed  CAS  Google Scholar 

  46. Kameda, T., Hatakeyama, S., Ma, Y.-Z., et al. (2002). Targeted elimination of the follicular label-retaining cells by photo-induced cell killing caused a defect on follicular renewal on mice. Genes to Cells, 7, 923–931.

    PubMed  CAS  Google Scholar 

  47. Greco, V., Chen, T., Rendl, M., et al. (2009). A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell, 4, 155–169.

    PubMed  CAS  Google Scholar 

  48. Wilson, A., Laurenti, E., Oser, G., et al. (2008). Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell, 135, 1118–1129.

    PubMed  CAS  Google Scholar 

  49. Humphreys, B. D. (2009). Slow-cycling cells in renal papilla: Stem cells awaken? Journal of the American Society of Nephrology, 20, 2277–2279.

    PubMed  Google Scholar 

  50. Runck, L. A., Kramer, M., Ciraolo, G., Lewis, A., & Guasch, G. (2010). Identification of epithelial label-retaining cells at the transition between the anal canal and the rectum in mice. Cell Cycle, 9, 3039–3045.

    PubMed  CAS  Google Scholar 

  51. Nakamura, M., & Ishikawa, O. (2008). The localization of label-retaining cells in mouse nails. Journal of Investigative Dermatology, 128, 728–730.

    PubMed  CAS  Google Scholar 

  52. Li, A., Simmons, P. J., & Kaur, P. (1998). Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype. Proceedings of the National Academy of Sciences of the United States of America, 95, 3902–3907.

    PubMed  CAS  Google Scholar 

  53. Tani, H., Morris, R. J., & Kaur, P. (2000). Enrichment for murine keratinocyte stem cells based on cell surface phenotype. Proceedings of the National Academy of Sciences of the United States of America, 97, 10960–10965.

    PubMed  CAS  Google Scholar 

  54. Michel, M., Török, N., Godbout, M.-J., et al. (1996). 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. Journal of Cell Science, 109, 1017–1028.

    PubMed  CAS  Google Scholar 

  55. Lyle, S., Christofidou-Solomidou, M., Liu, Y., Elder, D. E., Albelda, S., & Cotsarelis, G. (1998). The C8/144b monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells. Journal of Cell Sciences, 111, 3179–3188.

    CAS  Google Scholar 

  56. Liu, Y., Lyle, S., Yang, Z., & Cotsarelis, G. (2003). Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge. Journal of Investigative Dermatology, 121, 963–968.

    PubMed  CAS  Google Scholar 

  57. Matic, M., Evans, W. H., Brink, P. R., & Simon, M. (2002). Epidermal stem cells do not communicate through gap junctions. Journal of Investigative Dermatology, 118, 110–116.

    PubMed  CAS  Google Scholar 

  58. Matic, M., & Simon, M. (2003). Label-retaining cells (presumptive stem cells) of mice vibrissae do not express gap junction protein connexin 43. The Journal of Investigative Dermatology. Symposium Proceedings, 8, 91–95.

    CAS  Google Scholar 

  59. Albert, M. R., Foster, R. A., & Vogel, J. C. (2001). Murine epidermal label-retaining cells isolated by flow cytometry do not express the stem cell markers CD34, Sca-1, or Flk-1. Journal of Investigative Dermatology, 117, 943–948.

    PubMed  CAS  Google Scholar 

  60. Nowak, J. A., Polak, L., Pasolli, H. A., & Fuchs, E. (2008). Hair follicle stem cells are specified and function in early skin morphogenesis. Cell Stem Cell, 3, 33–43.

    PubMed  CAS  Google Scholar 

  61. Trempus, C. S., Morris, R. J., Bortner, C. D., et al. (2003). Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34. Journal of Investigative Dermatology, 120, 501–511.

    PubMed  CAS  Google Scholar 

  62. Morris, R. J., Fischer, Sm, & Slaga, T. J. (1986). Evidence that a slowly cycling subpopulation of adult murine epidermal cells retains carcinogen. Cancer Research, 46, 3061–3066.

    PubMed  CAS  Google Scholar 

  63. Morris, R. J., Coulter, K., Tryson, K., & Steinberg, S. R. (1997). Evidence that cutaneous carcinogen-initiated epithelial cells from mice are quiescent rather than actively cycling. Cancer Research, 57, 3435–3443.

    Google Scholar 

  64. Morris, R. J., Tryson, K., & Wu, K. Q. (2000). Evidence that epidermal targets of carcinogen action are found in the interfollicular epidermis or infundibulum as well as in the hair follicles. Cancer Research, 60, 226–229.

    PubMed  CAS  Google Scholar 

  65. Oro, A. E., Higgins, K. M., Hu, Z., Bonifas, J. M., Epstein, E. H., Jr., & Scott, M. P. (1997). Basal cell carcinomas in mice overexpressing sonic hedgehog. Science, 276, 817–821.

    PubMed  CAS  Google Scholar 

  66. Hutchin, M. E., Kariapper, M. S., Grachtchouk, M., et al. (2005). Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: Conditional skin tumorigenesis recapitulates the hair growth cycle. Genes & Development, 19(2), 214–223.

    CAS  Google Scholar 

  67. Kim, S. J., Cheung, S., & Hellerstein, M. K. (2004). Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon. American Journal of Physiology. Cell Physiology, 286, C1464–C1473.

    PubMed  CAS  Google Scholar 

  68. Poojan, S., & Kumar, S. (2011). Flow cytometry-based characterization of label-retaining stem cells following transplacental BrdU labeling. Cell Biology International, 35, 147–151.

    PubMed  Google Scholar 

  69. Cairns, J. (1975). Mutation, selection and cancer. Nature, 255, 197–200.

    PubMed  CAS  Google Scholar 

  70. Cairns, J. (2006). Cancer and the immortal strand hypothesis. Genetics, 174, 1069–1072.

    PubMed  CAS  Google Scholar 

  71. Potten, C. S. (2004). Keratinocyte stem cells, label-retaining cells and possible genome protection mechanisms. The Journal of Investigative Dermatology. Symposium Proceedings, 9, 183–195.

    CAS  Google Scholar 

  72. Potten, C. S., Owen, G., & Booth, D. (2002). Intestinal stem cells protect their genome by selective segregation of template DNA strands. Journal of Cell Science, 115(Pt 11), 2381–2388.

    PubMed  CAS  Google Scholar 

  73. Karpowicz, P., Morshead, C., Kam, A., et al. (2005). Support for the immortal strand hypothesis: Neural stem cells partition DNA strands asymmetrically in vitro. The Journal of Cell Biology, 170, 721–732.

    PubMed  CAS  Google Scholar 

  74. Shinin, V., Gayraud-Morel, B., Gome’s, D., & Tajbakhsh, S. (2006). Asymmetric division and cosegregation of template DNA strands in adult muscle satellite cells. Nature Cell Biology, 8, 677–687.

    PubMed  CAS  Google Scholar 

  75. Smith, G. H. (2005). Label-retaining epithelial cells in mouse mammary gland divide asymmetrically and retain their template DNA strands. Development, 132, 681–687.

    PubMed  CAS  Google Scholar 

  76. Booth, W. B., & Smith, G. H. (2006). Estrogen receptor-α and progesterone receptor are expressed in label-retaining mammary epithelial cells that divide asymmetrically and retain their template DNA strands. Breast Cancer Research, 8(4), R49.

    PubMed  Google Scholar 

  77. Bussard, K. M., Boulanger, C. A., Kittrell, F. S., Behbod, F., Medina, D., & Smith, G. H. (2010). Immortalized, premalignant epithelial cell populations contain long-lived, label-retaining cells that asymmetrically divide and retain their template DNA. Breast Cancer Research, 12, R86. doi:10.1186/bcr2754.

    PubMed  Google Scholar 

  78. Kiel, M. J., He, S., Ashkenazi, R., et al. (2007). Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature, 449, 238–242.

    PubMed  CAS  Google Scholar 

  79. Waghmare, S. K., Bansal, R., Lee, J., Zhang, Y. V., McDermitt, D. J., & Tumbar, T. (2008). Quantitative proliferation dynamics and random chromosome segregation of hair follicle stem cells. The EMBO Journal, 27, 1309–1320.

    PubMed  CAS  Google Scholar 

  80. Sotiropoulou, P. A., Candi, A., & Blanpain, C. (2008). The majority of multipotent epidermal stem cells do not protect their genome by asymmetrical chromosome segregation. Stem Cells, 26, 2964–2973.

    PubMed  CAS  Google Scholar 

  81. Lansdorp, P. M. (2007). Immortal strands? give me a break. Cell, 129, 1244–1247.

    PubMed  CAS  Google Scholar 

  82. Rando, T. A. (2007). The immortal strand hypothesis: Segregation and reconstruction. Cell, 129, 1239–1243.

    PubMed  CAS  Google Scholar 

  83. Blanpain, C., Lowry, W. E., Geoghegan, A., Polak, L., & Fuchs, E. (2004). Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell, 118, 635–648.

    PubMed  CAS  Google Scholar 

  84. Morris, R. J., Liu, Y., Marles, L., et al. (2004). Capturing and profiling adult hair follicle stem cells. Nature Biotechnology, 22, 411–417.

    PubMed  CAS  Google Scholar 

  85. Ito, M., Liu, Y., Yang, Z., et al. (2005). Stem cells in the hair follicle bulge contribute to wound healing but not to homeostasis of the epidermis. Nature Medicine, 11, 1351–1354.

    PubMed  CAS  Google Scholar 

  86. Levy, V., Lindon, C., Zheng, Y., Harfe, B. D., & Morgan, B. A. (2007). Epidermal stem cells arise from the hair follicle after wounding. The FASEB Journal, 21, 1358–1366.

    CAS  Google Scholar 

  87. Levy, V., Lindon, C., Harfe, B. D., & Morgan, B. A. (2005). Distinct stem cell populations regenerate the follicle and interfollicular epidermis. Developmental Cell, 9, 855–861.

    PubMed  CAS  Google Scholar 

  88. Langton, A. K., Herrick, S. E., & Headon, D. J. (2008). An extended epidermal response heals cutaneous wounds in the absence of a hair follicle stem cell contribution. Journal of Investigative Dermatology, 128, 1311–1318.

    PubMed  CAS  Google Scholar 

  89. Clayton, E., Doupé, D. P., Klein, A. M., Winton, D. J., Simons, B. D., & Jones, P. H. (2007). A single type of progenitor cell maintains normal epidermis. Nature, 44, 185–189.

    Google Scholar 

  90. Jaks, V., Barker, N., Kasper, M., et al. (2008). Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nature Genetics, 40, 1291–1299.

    PubMed  CAS  Google Scholar 

  91. Snippert, H. J., Haegebarth, A., Kasper, M., et al. (2010). Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science, 327, 1385–1389.

    PubMed  CAS  Google Scholar 

  92. Yang, J. S., Lavker, R. M., & Sun, T.-T. (1993). Upper human hair follicle contains a subpopulation of keratinocytes with superior in vitro proliferative potential. Journal of Investigative Dermatology, 101, 652–659.

    PubMed  CAS  Google Scholar 

  93. Jensen, K. B., & Watt, F. M. (2006). Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence. Proceedings of the National Academy of Sciences of the United States of America, 103, 11958–11963.

    PubMed  CAS  Google Scholar 

  94. Jensen, K. B., Collins, C. A., Nascimento, E., et al. (2009). Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis. Cell Stem Cell, 4, 427–439.

    PubMed  CAS  Google Scholar 

  95. Nijhof, J. G., Braun, K. M., Giangreco, A., et al. (2006). The cell-surface marker MTS24 identifies a novel population of follicular keratinocytes with characteristics of progenitor cells. Development, 133, 3027–3037.

    PubMed  CAS  Google Scholar 

  96. Bickenbach, J. R., & Holbrook, K. A. (1987). Label-retaining cells (LRCs) in human embryonic and fetal epidermis. Journal of Investigative Dermatology, 88, 42–46.

    PubMed  CAS  Google Scholar 

  97. Passegué, E., Wagers, A. J., Guiriato, S., Anderson, W., & Weissman, I. L. (2005). Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates. The Journal of Experimental Medicine, 202, 1599–1611.

    PubMed  Google Scholar 

  98. Gandarillas, A., & Watt, F. M. (1997). c-Myc promotes differentiation of human epidermal stem cells. Genes & Development, 11, 2869–2882.

    CAS  Google Scholar 

  99. Waikel, R. L., Kawachi, Y., Waikel, P. A., Wang, X. J., & Roop, D. R. (2001). Deregulated expression of c-Myc depletes epidermal stem cells. Nature Genetics, 28, 165–168.

    PubMed  CAS  Google Scholar 

  100. Saito, R. M., Perreault, A., Peach, B., Satterlee, J. S., & van den Heuvel, S. (2004). The CDC-14 phosphatase controls developmental cell-cycle arrest in C. elegans. Nature Cell Biology, 6, 777–783.

    PubMed  CAS  Google Scholar 

  101. MacRae, T. H. (2005). Diapause: Diverse states of developmental and metabolic arrest. Journal of Biological Research, 3, 3–14.

    CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the project “Development of High Technology Production for Regenerative Medicine”, No. 2010-218-02-172 of the Ministry of Education and Science of RF.

Conflict of interest statement

The authors declare no potential conflicts of interest.

Author information

Authors and Affiliations

  1. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia

    Vasily V. Terskikh, Andrey V. Vasiliev & Ekaterina A. Vorotelyak

Authors
  1. Vasily V. Terskikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrey V. Vasiliev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ekaterina A. Vorotelyak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ekaterina A. Vorotelyak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Terskikh, V.V., Vasiliev, A.V. & Vorotelyak, E.A. Label Retaining Cells and Cutaneous Stem Cells. Stem Cell Rev and Rep 8, 414–425 (2012). https://doi.org/10.1007/s12015-011-9299-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-011-9299-6

Keywords

Search

Navigation