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Discovery of HAP Stem Cells

  • Lingna Li
  • Robert M. HoffmanEmail author
Protocol
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Part of the Methods in Molecular Biology book series (MIMB, volume 1453)

Abstract

Cells expressing the stem cell marker, nestin, were selectively labeled in transgenic mice by placing green fluorescent protein (GFP) under the control of the nestin promoter in transgenic mice. In these transgenic mice, neural and other stem cells brightly expressed GFP. The mice were termed nestin-driven GFP (ND-GFP) mice. During early anagen or growth phase of the hair follicle, ND-GFP appeared in the permanent upper hair follicle immediately below the sebaceous glands in the follicle bulge. The relatively small, oval-shaped, nestin-expressing cells in the bulge area surrounded the hair shaft and were interconnected by short dendrites. The location of the nestin-expressing cells in the hair follicle varied with the hair cycle. During telogen or resting phase and in early anagen, the GFP-positive cells are mainly in the bulge area. However, in mid- and late-anagen, the GFP-expressing cells were located in the upper outer-root sheath as well as in the bulge area. The expression of the unique protein, nestin, in both neural stem cells and hair follicle stem cells, which suggested their relationship. The ND-GFP hair follicle stem cells were later termed hair-follicle-associated pluripotent (HAP) stem cells.

Key words

Hair follicle Bulge Nestin GFP 

References

  1. 1.
    Oshima H, Rochat A, Kedzia C, Kobayashi K, Barrandon Y (2001) Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 104:233–245CrossRefPubMedGoogle Scholar
  2. 2.
    Cotsarelis G, Sun T-T, Lavker RM (1990) Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61:1329–1337CrossRefPubMedGoogle Scholar
  3. 3.
    Taylor G, Lehrer MS, Jensen PJ, Sun T-T, Lavker RM (2000) Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 102:451–461CrossRefPubMedGoogle Scholar
  4. 4.
    Lendahl U, Zimmerman LB, McKay RDG (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60:585–595CrossRefPubMedGoogle Scholar
  5. 5.
    Zimmerman L, Parr B, Lendahl U, Cunningham M, McKay R, Gavin B et al (1994) Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron 12:11–24CrossRefPubMedGoogle Scholar
  6. 6.
    Yaworsky PJ, Kappen C (1999) Heterogeneity of neural progenitor cells revealed by enhancers in the nestin gene. Dev Biol 205:309–321CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Li L, Mignone J, Yang M, Matic M, Penman S, Enikolopov G et al (2003) Nestin expression in hair follicle sheath progenitor cells. Proc Natl Acad Sci U S A 100:9958–9961CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hoffman RM (2014) Nestin-expressing hair follicle-accessible-pluripotent (HAP) stem cells for nerve and spinal cord repair. Cells Tissues Organs 200:42–47Google Scholar
  9. 9.
    Amoh, Y., Li, L., Katsuoka, K., Penman, S., and Hoffman, R.M. Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons. Proc. Natl. Acad. Sci. USA 102, 5530–5534, 2005Google Scholar
  10. 10.
    Amoh, Y., Li, L., Campillo, R., Kawahara, K., Katsuoka, K., Penman, S., and Hoffman, R.M. Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves. Proc. Natl. Acad. Sci. USA 102, 17734–17738, 2005Google Scholar
  11. 11.
    Amoh, Y., Li, L., Katsuoka, K., and Hoffman, R.M. Multipotent hair follicle stem cells promote repair of spinal cord injury and recovery of walking function. Cell Cycle 7, 1865–1869, 2008Google Scholar
  12. 12.
    Mii, S., Doung, J., Tome, Y., Uchgonova, A., Liu, F., Amoh, Y., Saito, N., Katsuoka, K., and Hoffman, R.M. The role of hair follicle nestin-expressing tstem cells during whisker sensory-nerve growth in long-term 3D culture. J. Cell. Biochem. 114, 1674–1684, 2013Google Scholar
  13. 13.
    Yashiro, M., Mii, S., Aki, R., Hamada, Y., Arakawa, N., Kawahara, K., Hoffman, R.M., and Amoh, Y. From hair to heart: nestin-expressing hair-follicle-associated pluripotenet (HAP) stem cells differentiate to beating cardiac muscle cells. Cell Cycle 14, 2362–2366, 2015Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.AntiCancer Inc.San DiegoUSA
  2. 2.Department of SurgeryUniversity of California, San DiegoSan DiegoUSA

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