Molecular regulation of spermatogonial stem cell renewal and differentiation

Abstract

The intricate molecular and cellular interactions between spermatogonial stem cells (SSCs) and their cognate niche form the basis for life-long sperm production. To maintain long-term fertility and sustain sufficiently high levels of spermatogenesis, a delicate balance needs to prevail between the different niche factors that control cell fate decisions of SSCs by promoting self-renewal, differentiation priming or spermatogenic commitment of undifferentiated spermatogonia (A undiff ). Previously the SSC niche was thought to be formed primarily by Sertoli cells. However, recent research has indicated that many distinct cell types within the testis contribute to the SSC niche including most somatic cell populations and differentiating germ cells. Moreover, postnatal testis development involves maturation of somatic supporting cell populations and onset of cyclic function of the seminiferous epithelium. The stochastic and flexible behavior of A undiff further complicates the definition of the SSC niche. Unlike in invertebrate species, providing a simple anatomical description of the SSC niche in the mouse is therefore challenging. Rather, the niche needs to be understood as a dynamic system that is able to serve the long-term reproductive function and maintenance of fertility both under steady-state and during development plus regeneration. Recent data from us and others have also shown that A undiff reversibly transition between differentiation-primed and self-renewing states based on availability of niche-derived cues. This review focuses on defining the current understanding of the SSC niche and the elements involved in its regulation.Reproduction (2019) 158 R169-R187 J-A Mäkelä and R M Hobbs R170 Reproduction (2019) 158 R169-R187 https://rep.bioscientifica.com SSC niche in mice R171 https://rep.bioscientifica.com Reproduction (2019) 158 R169-R187 J-A Mäkelä and R M Hobbs R172 Reproduction (2019) 158 R169-R187 https://rep.bioscientifica.com SSC niche in mice R173 https://rep.bioscientifica.com Reproduction (2019) 158 R169-R187 J-A Mäkelä and R M Hobbs R174 Reproduction (2019) 158 R169-R187 https://rep.bioscientifica.com J-A Mäkelä and R M Hobbs R176 Reproduction (2019) 158 R169-R187

PRMT5 Is Involved in Spermatogonial Stem Cells Maintenance by Regulating Plzf Expression via Modulation of Lysine Histone Modifications

“…The differentially expressed genes associated with stemness maintenance, proliferation and the cell cycle in both control and Prmt5 -deficient SSCs were examined by real-time PCR and western blot analysis. Plzf , Oct4 , Nanos3 , and Gfra1 are well-characterized pluripotent factors that are important for the maintenance of SSC stemness ( Oatley and Brinster, 2008 ; Chen et al, 2017 ; Mäkelä and Hobbs, 2019 ). As shown in Figure 5 , the expression of Prmt5 was dramatically reduced in Prmt5 flox /flox ;Cre-ER TM SSCs treated with 1 μM tamoxifen compared to those treated with ethanol.…”

“…Spermatogonia contain a small population of germline-specific stem cells with the ability to self-renew and differentiation. The differentiation of spermatogonia is stimulated by both intrinsic and extrinsic factors, which subsequently generate differentiating spermatogonia, spermatocytes, spermatids, and mature sperm ( Chen and Liu, 2015 ; Mäkelä and Hobbs, 2019 ). In mammals, both genetic and epigenetic modifications are involved in the development of male germ cells.…”

Spermatogonial Stem Cells for In Vitro Spermatogenesis and In Vivo Restoration of Fertility

“…In contrast, some other markers of rodent spermatogonia and their progenitors may not be conserved in humans. For example, it remains to be explored whether certain markers of rodent spermatogonia such as RET [37], STRA8 [38], CDH1 [39], and NEUROG3 (NGN3) [40] are also present in human spermatogonia. Conversely, certain specific markers of human spermatogonia have not been observed in rodents.…”

Spermatogonial Stem Cells in Fish: Characterization, Isolation, Enrichment, and Recent Advances of In Vitro Culture Systems

“…In mammals, SSCs lie on the basement membrane of the seminiferous epithelium and are in contact with Sertoli cells, which control the fate of the SSCs via physical and paracrine interactions [4,[29][30][31]. In addition to Sertoli cells, peritubular myoid cells and Leydig cells may contribute soluble growth factors to the niche environment [32][33][34]. Mammalian SSCs are preferentially located in those areas of the seminiferous tubules near the interstitial tissue where Leydig cells and blood vessels reside (Figure 3) [33,[35][36][37][38].…”

“…In addition to Sertoli cells, peritubular myoid cells and Leydig cells may contribute soluble growth factors to the niche environment [32][33][34]. Mammalian SSCs are preferentially located in those areas of the seminiferous tubules near the interstitial tissue where Leydig cells and blood vessels reside (Figure 3) [33,[35][36][37][38]. Recent studies have shown that type A undifferentiated spermatogonia are uniformly distributed on the basement membrane of seminiferous mouse epithelium [39].…”