Letter
Nature 436, 1030-1034 (18 August 2005) | doi:10.1038/nature03894
ERM is required for transcriptional control of the spermatogonial stem cell niche
Chen Chen1, Wenjun Ouyang4, Vadim Grigura1, Qing Zhou5, Kay Carnes6, Hyunjung Lim3, Guang-Quan Zhao7, Silvia Arber8,9, Natasza Kurpios10, Theresa L. Murphy1, Alec M. Cheng4, John A. Hassell10, Varadaraj Chandrashekar11, Marie-Claude Hofmann12, Rex A. Hess6 and Kenneth M. Murphy1,2
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.
- Department of Pathology and Immunology,
- Howard Hughes Medical Institute,
- Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, Missouri 63110, USA
- Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080
- School of Molecular Biosciences, Washington State University, Pullman, Washington 99164, USA
- Department of Veterinary Biosciences, University of Illinois at Urbana–Champaign, Urbana, Illinois 61802, USA
- Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical School, Dallas, Texas 75390, USA
- Biozentrum, Department of Cell Biology, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland
- Friedrich Miescher Institute, Maulbeerstrasse 66, 4058- Basel, Switzerland
- Institute for Molecular Biology and Biotechnology, McMaster University, 1280 Main Street, Hamilton, Ontario L8S 4K1, Canada
- Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois, USA
- Department of Biology, The University of Dayton, 300 College Park, Dayton, Ohio 45469-2320, USA
Correspondence to: Kenneth M. Murphy1,2 Correspondence and requests for materials should be addressed to K.M.M. (Email: murphy@pathbox.wustl.edu).Full Affymetrix data sets have been deposited with the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) as accession series GSE2205.
Received 8 March 2005; Accepted 6 June 2005
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