Heterogeneous, dynamic, and stochastic nature of mammalian spermatogenic stem cells

Abstract

Mammalian testes produce a huge number of sperm over a long period. This process, essential for the continuity of life, depends on the delicate balance of self-renewal and differentiation of resident stem cells, termed spermatogenic (spermatogonial) stem cells or SSCs. SSCs have motivated many researchers to query their identity, behavior, and regulation in the tissue microenvironment. The study of SSCs has a long and prominent history: Taking advantage of the unique organization of the seminiferous tubules, and the accompanying seminiferous epithelial cycle and spermatogenic wave, intricate concepts of SSC dynamics were established from the early days. This is represented by the "A_s model" first published in 1971. Then, numerous technical breakthroughs including transplantation, stem cell culture, organ culture, intravital live-imaging, and lineage tracing have made SSCs an invaluable model for tissue stem cell research. Further progress is likely to come from emerging technologies, such as in vitro gametogenesis and single cell omics. An ensemble of these experimental systems has lead to the identification of the dynamic and heterogeneous nature of SSCs, underpinning their context-dependent and flexible behavior. In addition, active migration of SSCs over the open (or facultative) niche microenvironment of the seminiferous tubules is in stark contrast to stem cell regulations within anatomically defined niches such as in the Drosophila ovary and testis (see chapter "Germline stem cell homeostasis" by Nelson et al.). By revealing novel mechanisms of stem cell regulation, research on mouse spermatogenesis will continually make significant contributions to the understanding of general concepts in the tissue stem-cell field.

Keywords: Clonal behavior; Dynamics; Heterogeneity; Live-imaging; Mouse; Open niche; Spermatogenesis; Stem cells; Testis.