ERM is required for transcriptional control of the spermatogonial stem cell niche (original) (raw)

Nature volume 436, pages 1030–1034 (2005)Cite this article

Abstract

Division of spermatogonial stem cells1 produces daughter cells that either maintain their stem cell identity or undergo differentiation to form mature sperm. The Sertoli cell, the only somatic cell within seminiferous tubules, provides the stem cell niche through physical support and expression of surface proteins and soluble factors2,3. Here we show that the Ets related molecule4 (ERM) is expressed exclusively within Sertoli cells in the testis and is required for spermatogonial stem cell self-renewal. Mice with targeted disruption of ERM have a loss of maintenance of spermatogonial stem cell self-renewal without a block in normal spermatogenic differentiation and thus have progressive germ-cell depletion and a Sertoli-cell-only syndrome. Microarray analysis of primary Sertoli cells from ERM-deficient mice showed alterations in secreted factors known to regulate the haematopoietic stem cell niche. These results identify a new function for the Ets family transcription factors in spermatogenesis and provide an example of transcriptional control of a vertebrate stem cell niche.

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Acknowledgements

We thank M. White for blastocyst microinjections; X. Cheng for helpful discussion; B. Sleckman for targeting vector; D. Ornitz, M. Griswold and K. Sheehan for reagents and antibody production; and T. Jessell for help with ERM IRES-LacZ mice. J.A.H. acknowledges funding from the Canadian Breast Cancer Research Alliance, the Canadian Institutes of Health Research and the DOD Breast Cancer Research Program. N.A.K. was supported by a DOD Breast Cancer Research Program Scholarship. K.M.M. is an investigator of the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

  1. Department of Pathology and Immunology,
    Chen Chen, Vadim Grigura, Theresa L. Murphy & Kenneth M. Murphy
  2. Howard Hughes Medical Institute,
    Kenneth M. Murphy
  3. Department of Obstetrics and Gynecology, Washington University School of Medicine, Missouri, 63110, St Louis, USA
    Hyunjung Lim
  4. Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California, 94080
    Wenjun Ouyang & Alec M. Cheng
  5. School of Molecular Biosciences, Washington State University, Washington, 99164, Pullman, USA
    Qing Zhou
  6. Department of Veterinary Biosciences, University of Illinois at Urbana–Champaign, Illinois, 61802, Urbana, USA
    Kay Carnes & Rex A. Hess
  7. Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical School, Texas, 75390, Dallas, USA
    Guang-Quan Zhao
  8. Biozentrum, Department of Cell Biology, University of Basel, Klingelbergstrasse 70, 4056, Basel, Switzerland
    Silvia Arber
  9. Friedrich Miescher Institute, Maulbeerstrasse 66, 4058-, Basel, Switzerland
    Silvia Arber
  10. Institute for Molecular Biology and Biotechnology, McMaster University, 1280 Main Street, Ontario, L8S 4K1, Hamilton, Canada
    Natasza Kurpios & John A. Hassell
  11. Department of Physiology, Southern Illinois University School of Medicine, Illinois, Carbondale, USA
    Varadaraj Chandrashekar
  12. Department of Biology, The University of Dayton, 300 College Park, Ohio, 45469-2320, Dayton, USA
    Marie-Claude Hofmann

Authors

  1. Chen Chen
  2. Wenjun Ouyang
  3. Vadim Grigura
  4. Qing Zhou
  5. Kay Carnes
  6. Hyunjung Lim
  7. Guang-Quan Zhao
  8. Silvia Arber
  9. Natasza Kurpios
  10. Theresa L. Murphy
  11. Alec M. Cheng
  12. John A. Hassell
  13. Varadaraj Chandrashekar
  14. Marie-Claude Hofmann
  15. Rex A. Hess
  16. Kenneth M. Murphy

Corresponding author

Correspondence toKenneth M. Murphy.

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Competing interests

Full Affymetrix data sets have been deposited with the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) as accession series GSE2205. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

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Chen, C., Ouyang, W., Grigura, V. et al. ERM is required for transcriptional control of the spermatogonial stem cell niche.Nature 436, 1030–1034 (2005). https://doi.org/10.1038/nature03894

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