8 Male Germ-line Stem Cells

Abstract

Spermatogenesis is a classic stem cell system. Continuous production of highly differentiated, short-lived sperm is maintained throughout reproductive life by a small, dedicated population of male germ-line stem cells (GSCs). Male GSCs are unipotent, devoted solely to the generation of sperm, much like epidermal stem cells that give rise only to keratinocytes (see Chapter 19). As precursors of the spermatogonial lineage, male GSCs must maintain a balance between the production of mature sperm and the self-renewal of stem cell potential.

Male germ-line stem cells are defined by their function as persistent, clonogenic founders of differentiating germ cells. They can be identified by multiple criteria, including anatomical position within a niche in the testis and distinct behavioral and molecular phenotypes. Male GSCs exhibit many similarities to other stem cell systems. Spermatogonial stem cells are a rare, relatively quiescent population that lies in a protected region in the testis among support cells, which may regulate their behavior. Like all stem cells, male GSCs are the most resistant cells to irradiation or chemical damage. As with hematopoietic stem cells, spermatogonial stem cells in mammals are transplantable, with an ability to both expand the stem cell pool and to regenerate an entire depleted spermatogenic lineage. Spermatogonial stem cells also exhibit signature molecular features, such as high expression of β-1 integrin, much like epidermal and hematopoietic stem cells.

The function of male GSCs has broad implications for development, disease, and evolution. Spermatogenesis is fundamental for the propagation of species. Spermatogenic defects can result in infertility...