The "Community Effect" of spermatogonial stem cells (SSCs) and their descendants on the induction of the SSC niche: Perspectives and hypotheses.

Abstract

Since the first description of "stem cells" in spermatogenesis in 1885, our understanding of spermatogonial stem cells (SSCs) has evolved over time. Normal function of SSCs is critical for the survival of a species, and thus, a balanced control of SSC fate (self-renewal or commitment) is required to transmit genetic information adequately to future generations. A microenvironment that surrounds SSCs, the SSC niche, is widely considered to generate a dominant force for this balancing mechanism and "dictate" SSC fate. The components of the SSC niche are thought to be somatic cells, particularly Sertoli cells, and acellular substrates, such as the extracellular matrix. The aim of this chapter is to provide different perspectives into our current understanding of the SSC-niche relationship. Notably, as SSCs cannot be visualized unequivocally, our understanding of the SSC-niche communication has been underdeveloped. As a result, discussions presented here involve assumptions and speculations. Under this premise, I will discuss three hypotheses. First, SSCs and germ cells are the driving force of spermatogenesis and the fundamental constituents of the SSC niche. Second, the somatic niche provides a permissive environment that supports, rather than dictates, the functions of SSCs and their descendant germ cells. Third, SSCs and their niches communicate reciprocally to fine-tune the fate of SSCs while orchestrating spermatogenesis. The overarching concept is that SSCs induce their niches by forming a community of their descendant germ cells while somatic cells passively respond to the community. I will further attempt to apply this germ cell-dominant concept of SSC niche to human spermatogenesis, since the uniqueness of human spermatogenesis casts significant questions on the soma-dominant concept of SSC niche that has been generated using the mouse model.