Autologous Pluripotent Stem Cells Generated from Adult Mouse Testicular Biopsy

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  1. 1.

    Brinster, R. L., & Zimmermann, J. W. (1994). Spermatogenesis following male germ-cell transplantation. Proceedings of the National Academy of Sciences of the United States of America, 91(24), 11298–11302.

  2. 2.

    Clermont, Y. (1972). Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiological Reviews, 52(1), 198–236.

  3. 3.

    Conrad, S., Renninger, M., Hennenlotter, J., et al. (2008). Generation of pluripotent stem cells from adult human testis. Nature, 456(7220), 344–349.

  4. 4.

    Eckardt, S., Leu, N. A., Bradley, H. L., et al. (2007). Hematopoietic reconstitution with androgenetic and gynogenetic stem cells. Genes & Development, 21(4), 409–419.

  5. 5.

    Golestaneh, N., Kokkinaki, M., Pant, D., et al. (2009). Pluripotent stem cells derived from adult human testes. Stem Cells and Development, 18(8), 1115–1126.

  6. 6.

    Hanna, J., Wernig, M., Markoulaki, S., et al. (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science, 318(5858), 1920–1923.

  7. 7.

    He, Z., Kokkinaki, M., Jiang, J., Dobrinski, I., & Dym, M. (2010). Isolation, characterization, and culture of human spermatogonia. Biology of Reproduction, 82(2), 363–372.

  8. 8.

    Huangfu, D., Osafune, K., Maehr, R., et al. (2008). Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nature Biotechnology, 26(11), 1269–1275.

  9. 9.

    Huckins, C. (1971). The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation and maturation. The Anatomical Record, 169(3), 533–557.

  10. 10.

    Kanatsu-Shinohara, M., Inoue, K., Lee, J., et al. (2004). Generation of pluripotent stem cells from neonatal mouse testis. Cell, 119(7), 1001–1012.

  11. 11.

    Kanatsu-Shinohara, M., Ogonuki, N., Inoue, K., et al. (2003). Long-term proliferation in culture and germline transmission of mouse male germline stem cells. Biology of Reproduction, 69(2), 612–616.

  12. 12.

    Kazuki, Y., Hoshiya, H., Kai, Y., et al. (2008). Correction of a genetic defect in multipotent germline stem cells using a human artificial chromosome. Gene Therapy, 15(8), 617–624.

  13. 13.

    Kim, J. B., Sebastiano, V., Wu, G., et al. (2009). Oct4-induced pluripotency in adult neural stem cells. Cell, 136(3), 411–419.

  14. 14.

    Kim, J. B., Zaehres, H., Wu, G., et al. (2008). Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature, 454(7204), 646–650.

  15. 15.

    Ko, K., Arauzo-Bravo, M. J., Kim, J., Stehling, M., & Scholer, H. R. (2010). Conversion of adult mouse unipotent germline stem cells into pluripotent stem cells. Nature Protocols, 5(5), 921–928.

  16. 16.

    Ko, K., Arauzo-Bravo, M. J., Tapia, N., et al. (2010). Human adult germline stem cells in question. Nature, 465(7301), E1. discussion E3.

  17. 17.

    Ko, K., Reinhardt, P., Tapia, N., et al. (2011). Brief report: evaluating the potential of putative pluripotent cells derived from human testis. Stem Cells, 29(8), 1304–1309.

  18. 18.

    Ko, K., Tapia, N., Wu, G., et al. (2009). Induction of pluripotency in adult unipotent germline stem cells. Cell Stem Cell, 5(1), 87–96.

  19. 19.

    Kossack, N., Meneses, J., Shefi, S., et al. (2009). Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells. Stem Cells, 27(1), 138–149.

  20. 20.

    Kubota, H., Avarbock, M. R., & Brinster, R. L. (2004). Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proceedings of the National Academy of Sciences of the United States of America, 101(47), 16489–16494.

  21. 21.

    Lawson, K. A., & Hage, W. J. (1994). Clonal analysis of the origin of primordial germ cells in the mouse. Ciba Foundation Symposium, 182, 68–84. discussion 84–91.

  22. 22.

    Looijenga, L. H., Stoop, H., de Leeuw, H. P., et al. (2003). POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer Research, 63(9), 2244–2250.

  23. 23.

    Loya, K., Eggenschwiler, R., Ko, K., et al. (2009). Hepatic differentiation of pluripotent stem cells. Biological Chemistry, 390(10), 1047–1055.

  24. 24.

    Mann, J. R., Gadi, I., Harbison, M. L., Abbondanzo, S. J., & Stewart, C. L. (1990). Androgenetic mouse embryonic stem cells are pluripotent and cause skeletal defects in chimeras: implications for genetic imprinting. Cell, 62(2), 251–260.

  25. 25.

    McLaren, A. (2003). Primordial germ cells in the mouse. Developmental Biology, 262(1), 1–15.

  26. 26.

    Mizrak, S. C., Chikhovskaya, J. V., Sadri-Ardekani, H., et al. (2010). Embryonic stem cell-like cells derived from adult human testis. Human Reproduction, 25(1), 158–167.

  27. 27.

    Molyneaux, K. A., Stallock, J., Schaible, K., & Wylie, C. (2001). Time-lapse analysis of living mouse germ cell migration. Developmental Biology, 240(2), 488–498.

  28. 28.

    Nagano, M., Patrizio, P., & Brinster, R. L. (2002). Long-term survival of human spermatogonial stem cells in mouse testes. Fertility and Sterility, 78(6), 1225–1233.

  29. 29.

    Nakagawa, M., Koyanagi, M., Tanabe, K., et al. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature Biotechnology, 26(1), 101–106.

  30. 30.

    Nakane, A., Kojima, Y., Hayashi, Y., et al. (2005). Effect of testicular biopsy in childhood on spermatogenesis, fertility, and paternity in adulthood–a mouse model study. Urology, 66(3), 682–686.

  31. 31.

    Ogawa, T., Ohmura, M., Tamura, Y., et al. (2004). Derivation and morphological characterization of mouse spermatogonial stem cell lines. Archives of Histology and Cytology, 67(4), 297–306.

  32. 32.

    Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T., & Yamanaka, S. (2008). Generation of mouse induced pluripotent stem cells without viral vectors. Science, 322(5903), 949–953.

  33. 33.

    Resnick, J. L., Bixler, L. S., Cheng, L., & Donovan, P. J. (1992). Long-term proliferation of mouse primordial germ cells in culture. Nature, 359(6395), 550–551.

  34. 34.

    Seandel, M., James, D., Shmelkov, S. V., et al. (2007). Generation of functional multipotent adult stem cells from GPR125+ germline progenitors. Nature, 449(7160), 346–350.

  35. 35.

    Shi, Y. Q., Wang, Q. Z., Liao, S. Y., et al. (2006). In vitro propagation of spermatogonial stem cells from KM mice. Frontiers in Bioscience, 11, 2614–2622.

  36. 36.

    Stadtfeld, M., Apostolou, E., Akutsu, H., et al. (2010). Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature, 465(7295), 175–181.

  37. 37.

    Stevens, L. C. (1967). Origin of testicular teratomas from primordial germ cells in mice. Journal of the National Cancer Institute, 38(4), 549–552.

  38. 38.

    Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–676.

  39. 39.

    Tapia, N., Arauzo-Bravo, M. J., Ko, K., & Scholer, H. R. (2011). Concise review: challenging the pluripotency of human testis-derived ESC-like cells. Stem Cells, 29(8), 1165–1169.

  40. 40.

    Tegelenbosch, R. A., & de Rooij, D. G. (1993). A quantitative study of spermatogonial multiplication and stem cell renewal in the C3H/101 F1 hybrid mouse. Mutation Research, 290(2), 193–200.

  41. 41.

    Wernig, M., Meissner, A., Cassady, J. P., & Jaenisch, R. (2008). c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell, 2(1), 10–12.

  42. 42.

    Yu, J., Vodyanik, M. A., Smuga-Otto, K., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858), 1917–1920.

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We thank Jeanine Müller-Keuker for helping to generate Supplementary Fig. 1 and Anna Niehues for providing technical assistance with the experiments. This work was supported by the Max Planck Society, DFG grant SPP 1356 entitled “Pluripotency and Cellular Reprogramming” (SCHO 340/5-1), and BMBF grant entitled “Disease-specific iPS cells” (FKZ 01GN0811).

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Correspondence to Hans R. Schöler.

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The authors declare no potential conflicts of interest.

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Ko, K., Wu, G., Araúzo-Bravo, M.J. et al. Autologous Pluripotent Stem Cells Generated from Adult Mouse Testicular Biopsy. Stem Cell Rev and Rep 8, 435–444 (2012) doi:10.1007/s12015-011-9307-x

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  • Major Histocompatibility Complex
  • Teratoma
  • Pluripotent Cell
  • Testicular Cell
  • Oct4 Expression