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Nature 440, 1199-1203 (27 April 2006) | doi:10.1038/nature04697; Received 21 November 2005; Accepted 7 March 2006; Published online 24 March 2006

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Pluripotency of spermatogonial stem cells from adult mouse testis

Kaomei Guan1,4, Karim Nayernia2,4, Lars S. Maier1, Stefan Wagner1, Ralf Dressel3, Jae Ho Lee2, Jessica Nolte2, Frieder Wolf1, Manyu Li2, Wolfgang Engel2 & Gerd Hasenfuss1

  1. Department of Cardiology and Pneumology, Heart Center, Georg-August-University of Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany
  2. Institute of Human Genetics and
  3. Department of Cellular and Molecular Immunology, Georg-August-University of Göttingen, Heinrich-Dücker-Weg 12, 37073 Göttingen, Germany
  4. These authors contributed equally to this work

Correspondence to: Wolfgang Engel2Gerd Hasenfuss1 Correspondence and requests for materials should be addressed to G.H. (Email: hasenfus@med.uni-goettingen.de) or W.E. (Email: wengel@gwdg.de).

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Embryonic germ cells as well as germline stem cells from neonatal mouse testis are pluripotent and have differentiation potential similar to embryonic stem cells1, 2, suggesting that the germline lineage may retain the ability to generate pluripotent cells. However, until now there has been no evidence for the pluripotency and plasticity of adult spermatogonial stem cells (SSCs), which are responsible for maintaining spermatogenesis throughout life in the male3. Here we show the isolation of SSCs from adult mouse testis using genetic selection, with a success rate of 27%. These isolated SSCs respond to culture conditions and acquire embryonic stem cell properties. We name these cells multipotent adult germline stem cells (maGSCs). They are able to spontaneously differentiate into derivatives of the three embryonic germ layers in vitro and generate teratomas in immunodeficient mice. When injected into an early blastocyst, SSCs contribute to the development of various organs and show germline transmission. Thus, the capacity to form multipotent cells persists in adult mouse testis. Establishment of human maGSCs from testicular biopsies may allow individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells. Furthermore, these cells may provide new opportunities to study genetic diseases in various cell lineages.

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