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Pluripotency of spermatogonial stem cells from adult mouse testis

Nature volume 440, pages 1199–1203 (2006)Cite this article

Abstract

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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Figure 1: Cellular and molecular characterization of cultured SSCs and maGSCs.
Figure 2: RT–PCR analysis of lineage-specific transcription factors and genes.
Figure 3: Mesoderm differentiation of maGSCs.
Figure 4: Differentiation of maGSCs in vitro and in vivo.

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Acknowledgements

We thank A. Cierpka, D. Meyer, S. Wolf, B. Sadowski, I. Schwandt, C. Müller and S. Burkhardt for technical assistance. We thank M. Schindler, H. Riedesel and S. Wolf for their assistance in the generation of transgenic mice, G. Wulf for help with FACS analysis, and B. Hemmerlein for the analysis of teratomas. This work was supported by grants from the Georg-August-University of Göttingen (Forschungsförderungsprogramm Stammzellen) to K.G. and K.N., and a DFG grant (Emmy-Noether Program) to L.S.M. Author Contributions K.G., G.H., K.N. and W.E. conceived and designed the experiments and performed the data analysis and controls. K.G., K.N., L.S.M., S.W., R.D., J.H.L., J.N., F.W. and M.L. performed the experiments, and K.G., G.H., K.N. and W.E. wrote the paper.

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Author notes

  1. Kaomei Guan and Karim Nayernia: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Cardiology and Pneumology, Heart Center, Georg-August-University of Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

    Kaomei Guan, Lars S. Maier, Stefan Wagner, Frieder Wolf & Gerd Hasenfuss

  2. Institute of Human Genetics,

    Karim Nayernia, Jae Ho Lee, Jessica Nolte, Manyu Li & Wolfgang Engel

  3. Department of Cellular and Molecular Immunology, Georg-August-University of Göttingen, Heinrich-Dücker-Weg 12, 37073, Göttingen, Germany

    Ralf Dressel

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Correspondence to Wolfgang Engel or Gerd Hasenfuss.

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Supplementary information

Supplementary Methods

Full description of methods and analysis used in this study. (DOC 45 kb)

Supplementary Figures and Figure Legends

This file contains Supplementary Figures 1-6. (PDF 1020 kb)

Supplementary Tables

This file contains Supplementary Tables 1-4. Analysis of DNA microsatellite markers in the established cell lines as compared to the other cells cultured in the same facility. (DOC 333 kb)

Supplementary Video 1

Spontaneously and rhythmically beating cells in culture. (MPG 2757 kb)

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Guan, K., Nayernia, K., Maier, L. et al. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 440, 1199–1203 (2006). https://doi.org/10.1038/nature04697

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