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Defining the Phenotype and Function of Mammalian Spermatogonial Stem Cells

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The Biology of Mammalian Spermatogonia

Abstract

Spermatogonial stem cells (SSCs) are a subpopulation of undifferentiated spermatogonia that maintain spermatogenesis throughout adult life and are essential for male fertility. At each cell division, an SSC produces daughter cells that will either self-renew to produce more SSCs or initiate differentiation to ultimately produce spermatozoa. Consequently, fertility throughout the mammalian male lifespan depends on formation of a foundational SSC pool and then balanced SSC self-renewal and differentiation once steady-state spermatogenesis is achieved. Fundamental studies of SSCs, however, are complicated by their extraordinary rarity in the adult testis (0.01%) and lack of definitive molecular markers that have allowed their prospective identification at any stage of testis development in any species. Despite these challenges, powerful experimental strategies such as transplantation and lineage tracing, which provide retrospective stem cell assessments, have revealed considerable phenotypic information about SSCs over the past two decades. This chapter provides an overview of the key phenotypic and functional characteristics of SSCs, the relative value of differing assessment methods, and the best-substantiated markers of SSCs. Particular emphasis will be placed on emerging technologies, such as single-cell molecular profiling and the use of ID4 reporters, which are facilitating the first prospective, comprehensive molecular characterizations of SSCs that will transform our understanding of the underlying regulatory framework controlling their function.

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Acknowledgements

The Hermann lab is supported by NIH grants K99/R00 HD062687, R21 HD078916, R01 HD90007, P30 GM092334 (PI: John McCarrey), NSF grant DBI-1337513, the Max and Minnie Tomerlin Voelcker Fund, the Helen Freeborn Kerr Foundation, and the University of Texas at San Antonio. We also gratefully acknowledge ongoing assistance of our work by the UTSA Computational System Biology Core, Genomics Core and Immune Defense Core (NIH G12 MD007591), the University of Texas Health Science Center at San Antonio (UTHSCSA) Flow Cytometry Shared Resource Facility (supported by NIH P30 CA054174 and UL1 RR025767), and the Southwest National Primate Research Center (NIH P51 OD011133).

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Authors and Affiliations

  1. Department of Biology, The University of Texas at San Antonio, One UTSA Circle, San Antonio, TX, 78249, USA

    Kazadi N. Mutoji & Brian P. Hermann Ph.D.

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  1. Kazadi N. Mutoji
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  2. Brian P. Hermann Ph.D.
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Correspondence to Brian P. Hermann Ph.D. .

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Editors and Affiliations

  1. Centre for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington, USA

    Jon M. Oatley

  2. School of Molecular Biosciences, Washington State University, Pullman, Washington, USA

    Michael D. Griswold

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Mutoji, K.N., Hermann, B.P. (2017). Defining the Phenotype and Function of Mammalian Spermatogonial Stem Cells. In: Oatley, J., Griswold, M. (eds) The Biology of Mammalian Spermatogonia. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7505-1_4

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