Stem Cell Reviews

, Volume 4, Issue 4, pp 256–260

Epidermal Neural Crest Stem Cells (EPI-NCSC) and Pluripotency

Article

Abstract

This article serves three purposes. We summarize current knowledge of the origin and characteristics of EPI-NCSC, review their application in a mouse model of spinal cord injury, and we present new data that highlight aspects of pluripotency of EPI-NCSC. EPI-NCSC are multipotent stem cells, which are derived from the embryonic neural crest and are located in the bulge of hair follicles. EPI-NCSC can undergo self-renewal and they are able to generate all major neural crest derivatives, including neurons, nerve supporting cells, smooth muscle cells, bone/cartilage cells and melanocytes. Despite their ectodermal origin, neural crest cells can also generate cell types that typically are derived from mesoderm. We were therefore interested in exploring aspects of EPI-NCSC pluripotency. We here show that EPI-NCSC can fuse with adult skeletal muscle fibers and that incorporated EPI-NCSC nuclei are functional. Furthermore, we show that adult skeletal muscle represents an environment conducive to long-term survival of neurogenic EPI-NCSC. Genes used to create induced pluripotent stem (iPS) cells are present in our EPI-NCSC longSAGE gene expression library. Here we have corroborated this notion by real-time PCR. Our results show similarities in the expression of Myc, Klf4, Sox2 and Lin28 genes between EPI-NCSC and embryonic stem cells (ESC). In contrast there were major differences in Nanog and Pou5f1 (Oct-4) expression levels between EPI-NCSC and ESC, possibly explaining why EPI-NCSC are not tumorigenic. Overall, as embryonic remnants in an adult location EPI-NCSC show several attractive characteristics for future cell replacement therapy and/or biomedical engineering: Due to their ability to migrate, EPI-NCSC can be isolated as a highly pure population of multipotent stem cells by minimally-invasive procedures. The cells can be expanded in vitro into millions of stem cells/progenitors and they share some characteristics with pluripotent stem cells without being tumorigenic. Since the patients’ own EPI-NCSC could be used for autologous transplantation, this would avoid graft rejection.

Keywords

EPI-NCSC Neural crest Skeletal muscle Neuron Sox10 Myc Klf4 Sox2 Lin28 Oct-4 Pou5f1 Nanog iPS cell 

References

  1. 1.
    Duff, R. S., Langtimm, C. J., Richardson, M. K., & Sieber-Blum, M. (1991). In vitro clonal analysis of progenitor cell patterns in dorsal root and sympathetic ganglia of the quail embryo. Developmental Biology, 147, 451–459.PubMedCrossRefGoogle Scholar
  2. 2.
    Gibbs, C. P., Kukekov, V. G., Reith, J. D., Tchigrinova, O., Suslov, O. N., Scott, E. W., et al. (2005). Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia, 7, 967–976.PubMedCrossRefGoogle Scholar
  3. 3.
    Hu, Y. F., Zhang, Z. J., & Sieber-Blum, M. (2006). An epidermal neural crest stem cell (EPI-NCSC) molecular signature. Stem Cells, 24, 2692–2702 Epub 2006 Aug 24.PubMedCrossRefGoogle Scholar
  4. 4.
    Ito, K., & Sieber-Blum, M. (1993). Pluripotent and developmentally restricted neural-crest-derived cells in posterior visceral arches. Developmental Biology, 156, 191–200.PubMedCrossRefGoogle Scholar
  5. 5.
    Joseph, N. M., Mukouyama, Y. S., Mosher, J. T., Jaegle, M., Crone, S. A., Dormand, E. L., et al. (2004). Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells. Development, 131, 5599–5612 Epub 2004 Oct 20.PubMedCrossRefGoogle Scholar
  6. 6.
    Kruger, G. M., Mosher, J. T., Bixby, S., Joseph, N., Iwashita, T., & Morrison, S. J. (2002). Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron, 35, 657–669.PubMedCrossRefGoogle Scholar
  7. 7.
    Lee, J., Kim, J. Y., Kang, I. Y., Kim, H. K., Han, Y. M., & Kim, J. (2007). The EWS-Oct-4 fusion gene encodes a transforming gene. Biochemical Journal, 406, 519–526.PubMedCrossRefGoogle Scholar
  8. 8.
    Le Douarin, N. M., & Kalcheim, C. (Eds.) (1999). The Neural Crest. Cambridge and New York: Cambridge University Press.Google Scholar
  9. 9.
    Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448, 313–317 Epub 2007 Jun 6.PubMedCrossRefGoogle Scholar
  10. 10.
    Piestun, D., Kochupurakkal, B. S., Jacob-Hirsch, J., Zeligson, S., Koudritsky, M., Domany, E., et al. (2006). Nanog transforms NIH3T3 cells and targets cell-type restricted genes. Biochemical and biophysical research communications, 343, 279–285 Epub 2006 Mar 6.PubMedCrossRefGoogle Scholar
  11. 11.
    Rendl, M., Lewis, L., & Fuchs, E. (2005). Molecular dissection of mesenchymal-epithelial interactions in the hair follicle. PLoS Biology, 3(11), e331 Epub 2005 Sep 20, 2005 Nov..PubMedCrossRefGoogle Scholar
  12. 12.
    Richardson, M. K., & Sieber-Blum, M. (1993). Pluripotent neural crest cells in the developing skin of the quail embryo. Developmental Biology, 157, 348–358.PubMedCrossRefGoogle Scholar
  13. 13.
    Santagata, S., Ligon, K. L., & Hornick, J. L. (2007). Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors. American Journal of Surgical Pathology, 31, 836–845.PubMedCrossRefGoogle Scholar
  14. 14.
    Sieber-Blum, M., & Grim, M. (2004). The adult hair follicle: cradle for pluripotent neural crest stem cells. Birth Defects Research. Part C, Embryo Today, 72, 162–172.CrossRefGoogle Scholar
  15. 15.
    Sieber-Blum, M., Grim, M., Hu, Y. F., & Szeder, V. (2004). Pluripotent neural crest stem cells in the adult hair follicle. Development Dynamics, 231, 258–269.CrossRefGoogle Scholar
  16. 16.
    Sieber-Blum, M., Schnell, L., Grim, M., Hu, Y. F., Schneider, R., & Schwab, M. E. (2006). Characterization of epidermal neural crest stem cell (EPI-NCSC) grafts in the lesioned spinal cord. Molecular and Cellular Neurosciences, 32, 67–81 Epub 2006 Apr 19.PubMedCrossRefGoogle Scholar
  17. 17.
    Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–676 Epub 2006 Aug 10.PubMedCrossRefGoogle Scholar
  18. 18.
    Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., et al. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature, 448, 318–324 Epub 2007 Jun 6.PubMedCrossRefGoogle Scholar
  19. 19.
    Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318, 1917–1920 Epub 2007 Nov 20.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press 2008

Authors and Affiliations

  1. 1.Institute of Human Genetics and North East England Stem Cell Institute, Newcastle University, International Centre for LifeNewcastle upon TyneUK
  2. 2.Department of Cell BiologyNeurobiology and Anatomy, Medical College of WisconsinMilwaukeeUSA

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