Abstract
Generation of induced pluripotent stem cells from somatic cells by the expression of defined transcription factors has created new opportunities for the development of patient-specific therapies. Thus far, the generation of iPSCs has been performed from a variety of somatic sources. However, keratinocytes from either skin biopsies or plucked hair have shown significantly higher reprogramming efficiencies when compared to other easily accessible patient samples (e.g. a 100-fold higher reprogramming efficiency than fibroblasts). In this chapter we will summarize what we have learned after many years of intense research in both the hair follicle stem cell (SC) and iPSCs fields. First, we will focus on reviewing the current knowledge of hair follicle as a source of adult SCs for cell therapy. Second, we will discuss the future challenges in utilizing hair follicle SCs for regenerative medicine. Third, we will consider the benefits of utilizing iPSCs for cell therapy. Finally, we will provide a detailed a step-by-step protocol for the generation of human iPSCs from keratinocytes derived from a single plucked hair sample.
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- cMyc:
-
Avian myelocytomatosis viral oncogene homolog
- CFE:
-
Colony formation efficiency
- ES:
-
Embryonic stem
- ESCs:
-
Embryonic stem cells
- FACS:
-
Fluorescence activated cell-sorting
- Fbx15:
-
F-box 15
- hESC:
-
Human embryonic stem cells
- H2B-GFP:
-
Histone 2B-green fluorescent protein
- HMG:
-
High motility group
- ICM:
-
Inner cell mass
- iPSCs:
-
Induced pluripotent stem cells
- IRS:
-
Inner root sheath
- K15:
-
Cytokeratin 15
- KiPSCs:
-
Human iPSCs derived from keratinocytes
- Klf4:
-
Krüppel-like factor 4
- Lgr5:
-
Leucine-rich repeat-containing G protein-coupled receptor 5
- LRC:
-
Labelling retaining cell
- MEFs:
-
Mouse embryonic fibroblasts
- Oct4:
-
Octamer-binding transcription factor 4
- ORS:
-
Outer root sheath
- SC:
-
Stem cell
- Sox2:
-
Sry-related HMG box 2
References
Aasen, T., Raya, A., Barrero, M.J., Garreta, E., Consiglio, A., Gonzalez, F., Vassena, R., Bilic, J., Pekarik, V., Tiscornia, G., Edel, M., Boue, S. and Izpisua Belmonte, J.C., 2008. Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnology 26, 1276–1284.
Aasen, T. and Izpisúa Belmonte, J.C., 2010. Isolation and cultivation of human keratinocytes from skin or plucked hair for the generation of induced pluripotent stem cells. Nature Protocols 5, 371–382.
Amoh, Y., Li, L., Katsuoka, K., Penman, S. and Hoffman, R.M., 2005. Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons. Proceedings of the National Academy of Sciences of the United States of America 102, 5530–5534.
Amoh, Y., Li, L., Yang, M., Moossa, A.R., Katsuoka, K., Penman, S. and Hoffman, R.M., 2004. Nascent blood vessels in the skin arise from nestin.expressing hair-follicle cells. Proceedings of the National Academy of Sciences of the United States of America 101, 13291–13295.
Boue, S., Paramonov, I., Barrero, M.J. and Izpisúa Belmonte, J.C., 2010. Analysis of human and mouse reprogramming of somatic cells to induced pluripotent stem cells. what is in the plate? PLoS ONE 5, 12664.
Cotsarelis, G., 2006. Epithelial stem cells: a folliculocentric view. Journal of Investigative Dermatology 126, 1459–1468.
Cotsarelis, G., Sun, T.T. and 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.
Egli, D., Rosains, J., Birkhoff, G. and Eggan, K., 2007. Developmental reprogramming after chromosome transfer into mitotic mouse zygotes. Nature 447, 679–685.
Fuchs, E., 2009. The tortoise and the hair: slow-cycling cells in the stem cell race. Cell 137, 811–819.
Hochedlinger, K. and Plath, K., 2009. Epigenetic reprogramming and induced pluripotency. Development 136, 509–523.
Hoffman, RM., 2006. The pluripotency of hair follicle stem cells. Cell Cycle 5, 232–233.
Huangfu, D., Osafune, K., Maehr, R., Guo, W., Eijkelenboom, A., Chen, S., Muhlestein, W. and Melton, D.A., 2008. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nature Biotechnology 26, 1269–1275.
Ito, M., Liu, Y., Yang, Z., Nguyen, J., Liang, F., Morris, R.J. and Cotsarelis, G., 2005. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nature Medicine 11, 1351–1354.
Jaks, V., Barker, N., Kasper, M, Van Es, J.H., Snippert, H.J., Clevers, H. and Toftgard, R., 2008. Lrg5 marks cycling, yet long-lived, hair-follicle stem cells. Nature Genetics 40, 1291–1299.
Levy, V., Lindon, C., Harfe, B.D. and Morgan, B.A., 2005. Distinct stem cell populations regenerate the follicle and interfollicular epidermis. Developmental Cell 9, 855–861.
Limat, A., French, L.E., Blal, L., Saurat, J.H., Hunziker, T. and Salomon, D., 2003. Organotypic cultures of autologous hair follicle keratinocytes for the treatment of recurrent leg ulcers. Journal of the American Academy of Dermatology 48, 207–214.
Liu, Y., Lyle, S., Yang, Z. and Cotsarelis, G., 2003. Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge. Journal of Investigative Dermatology 121, 963–968.
Lyle, S., Christofidou-Solomidou, M., Liu, Y., Elder, D.E., Albelda, S. and Cotsarelis, G., 1998. The C8/144B monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells. Journal of Cell Science 111, 3179–3188.
Morris, R.J., Liu, Y., Marles, L., Yang, Z., Trempus, C., Li, S., Lin, J.S., Sawicki, J.A. and Cotsarelis, G., 2004. Capturing and profiling adult hair follicle stem cells. Nature Biotechnology 22, 411–417.
Ohyama, M., 2007. Hair follicle bulge: a fascinating reservoir of epithelial stem cells. Journal of Dermatological Science 46, 81–89.
Ohyama, M., Terunuma, A., Tock, C.L., Radonovich, M.F., Pise-Masison, C.A., Hopping S.B., Brady, J.N., Udey, M.C. and Vogel, J.C., 2006. Characterization and isolation of stem cell-enriched human hair follicle bulge cells. The Journal of Clinical Investigation 116, 249–260.
Oshima, H., Rochat, A., Kedzia, C., Kobayashi, K. and Barrandon, Y., 2001. Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 104, 233–245.
Selvaraj, V., Plane J.M., Williams A.J. and Deng, W., 2010. Switching cell fate: the remarkable rise of induced pluripotent stem cells and lineage reprogramming technologies. Trends in Biotechnology 28, 214–23.
Snippert, H.J., Haegebarth, A., Kasper, M., Jaks, V., Van Es, J.H., Barker, N., Van de Wetering, M., Van den Born, M., Begthel, H., Vries, R.G., Stange, D.E., Toftgard, R. and Clevers H., 2010. Lrg6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science 327, 1385–1389.
Takahashi, K. and Yamanaka, S., 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676.
Taylor, G., Lehrer, M.S., Jensen, P.J., Sun, T.T. and Lavker, R.M., 2000. Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 102, 451–461.
Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S. and Jones J.M., 1998. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145–1147.
Trempus, C.S., Morris, R.J., Bortner, C.D., Cotsarelis, G., Faircloth, R.S., Reece, J.M. and Tennant, R.W., 2003. Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34. Journal of Investigative Dermatology 120, 501–511.
Tumbar, T., Guasch, G., Greco, V., Blanpain, C., Lowry, W.E., Rendl, M. and Fuchs, E., 2004. Defining the epithelial stem cell niche in skin. Science 303, 359–363.
Yamanaka, S. and Blau, B.H, 2010. Nuclear reprogramming to a pluripotent state by three approaches. Nature 465, 704–712.
Yamanaka, S., 2007. Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell 1, 39–49.
Yu, H., Fang, D., Kumar, SM., Li, L., Nguyen, TK., Acs, G., Herlyn, M. and Xu, X., 2006. Isolation of a novel population of multipotent adult stem cells from human hair follicle. American Journal of Pathology 168, 1879–1888.
Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., Slukvin, I.I. and Thomson, J.A., 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920.
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Montserrat, N., Belmonte, J.C.I. (2012). Plucked hair: how to get stem cells and induced pluripotent stem cells for future clinical applications. In: Preedy, V.R. (eds) Handbook of hair in health and disease. Human Health Handbooks no. 1, vol 1. Wageningen Academic Publishers. https://doi.org/10.3920/978-90-8686-728-8_9
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DOI: https://doi.org/10.3920/978-90-8686-728-8_9
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