Spermatogonial Stem Cells

Oatley, Jon M.; Brinster, Ralph L.

doi:10.1016/s0076-6879(06)19011-4

Cited by 165 publications

(155 citation statements)

References 47 publications

Supporting

Mentioning

152

Contrasting

Order By: Relevance

“…The rarity of SSC in the testes (0.03% of all germ cells in the adult mouse testes [1]) and the lack of definitive markers make the in vivo study of SSCs challenging. Nevertheless, results of long-term culture of SSCs and experiments on their functional transplantation, in which they have been shown to reestablish spermatogenesis, have greatly enhanced our understanding of their characteristics and regulation [2,3]. A culture of mouse THY1+ germ cells in serum-free medium supplemented with glial cell line-derived neurotrophic factor (GDNF) and basic fibroblast growth factor (bFGF) supports the expansion of SSCs for extended periods of time [4], facilitating molecular and biochemical analyses of SSC self-renewal and division.…”

Section: Introductionmentioning

confidence: 99%

GABA exists as a negative regulator of cell proliferation in spermaogonial stem cells

Zheng

et al. 2013

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

γ-amino butyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system. GABA is also found in many peripheral tissues, where it has important functions during development. Here, we identified the existence of the GABA system in spermatogonial stem cells (SSCs) and found that GABA negatively regulates SSC proliferation. First, we demonstrated that GABA and its synthesizing enzymes were abundant in the testes 6 days postpartum (dpp), suggesting that GABA signaling regulates SSCs function in vivo. In order to directly examine the effect of GABA on SSC proliferation, we then established an in vitro culture system for long-term expansion of SSCs. We showed that GABA A receptor subunits, including α1, α5, β1, β2, β3 and γ3, the synthesizing enzyme GAD67, and the transporter GAT-1, are expressed in SSCs. Using phosphorylated histone H3 (pH3) staining, we demonstrated that GABA or the GABA A R-specific agonist muscimol reduced the proliferation of SSCs. This GABA regulation of SSC proliferation was shown to be independent of apoptosis using the TUNEL assay. These results suggest that GABA acts as a negative regulator of SSC proliferation to maintain the homeostasis of spermatogenesis in the testes.

show abstract

Section: Introductionmentioning

confidence: 99%

GABA exists as a negative regulator of cell proliferation in spermaogonial stem cells

Zheng

et al. 2013

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

show abstract

“…Self-renewing SSC Cultures-Cultures of self-renewing SSCs were established from Thy1 MACS selected 6 -8 days postpartum (dpp) donor B6.129S7-Gtrosa26 (designated Rosa; The Jackson Laboratory) male mice as previously described (16). Cultures were maintained in serum-free media with the addition of GDNF (20 ng/ml), Gfr␣1 (150 ng/ml), and basic fibroblast growth factor (1 ng/ml).…”

Section: Methodsmentioning

confidence: 99%

Glial Cell Line-derived Neurotrophic Factor Regulation of Genes Essential for Self-renewal of Mouse Spermatogonial Stem Cells Is Dependent on Src Family Kinase Signaling

Oatley¹,

Avarbock

Brinster

2007

Journal of Biological Chemistry

Self Cite

278

292

View full text Add to dashboard Cite

Self-renewal and differentiation by spermatogonial stem cells (SSCs) is the foundation for continual spermatogenesis. SSC self-renewal is dependent on glial cell line-derived neurotrophic factor (GDNF); however, intracellular mechanisms stimulated by GDNF in SSCs are unknown. To investigate these mechanisms we utilized a culture system that maintains a mouse undifferentiated germ cell population enriched for self-renewing SSCs. In these cultures mRNA for the transcription factors Bcl6b, Erm, and Lhx1 are up-regulated by GDNF and decreased in its absence. The expression of all three molecules was further identified in undifferentiated spermatogonia in vivo. Using small interfering RNA to reduce expression and transplantation to quantify stem cell numbers, Bcl6b, Erm, and Lhx1 were shown to be important for SSC maintenance in vitro. Next, GDNF was shown to activate both Akt and Src family kinase (SFK) signaling in SSCs, and culture of SSCs with inhibitors to Akt or SFKs followed by transplantation analysis showed significant impairment of SSC maintenance in vitro. Apoptosis analysis revealed a significant increase in the percentage of apoptotic cells when Akt, but not SFK, signaling was impaired, indicating that multiple signaling pathways are responsible for SSC selfrenewal and survival. Biochemical and gene expression experiments revealed that GDNF up-regulated expression of Bcl6b, Erm, and Lhx1 transcripts is dependent on SFK signaling. Overall, these data demonstrate that GDNF up-regulation of Bcl6b, Erm, and Lhx1 expression through SFK signaling is a key component of the intracellular mechanism for SSC self-renewal.In mammals several tissue systems rely on the function of a small undifferentiated adult stem cell population. The biological function of these cells is to preserve tissue homeostasis by providing differentiated cells while at the same time undergoing self-renewal to ensure that a constant supply of new stem cells is available. These two capabilities, self-renewal and differentiation, are often referred to as fate decisions and are the basis for how adult stem cells are defined. Some adult stem cell-dependent tissues include the epidermis, intestinal epithelium, bone marrow, and testis. The testis is one of the most productive systems, generating millions of sperm each day.Spermatogenesis, the process of sperm production, is a classic stem cell-dependent system in which external niche stimuli and internal gene expression regulate self-renewal and differentiation of spermatogonial stem cells (SSCs).3 Currently, very little is known about mechanisms regulating these SSC fate decisions, yet deciphering them is important for understanding male fertility and general adult stem cell biology. Study of SSC biology has been hampered because of their rarity in the testis and lack of specific markers for their isolation.The mammalian testis contains several different germ cell populations. SSCs are present in the undifferentiated spermatogonia population and are often referred to as A single (A s ) spermatogo...

show abstract

“…The numbers of these stem cells in testes is approximately 0.03 % of the total testicular cell population in the adult mouse [28,36]. Additionally, the establishment and maintenance of a niche's microenvironment in the seminiferous tubules of the testis is important to regulate the SSC population and its function [4].…”

Section: Introductionmentioning

confidence: 99%

Behavior of mouse spermatogonial stem-like cells on an electrospun nanofibrillar matrix

Malek

Kohram

Shahverdi

et al. 2012

J Assist Reprod Genet

View full text Add to dashboard Cite

Purpose Spermatogonial stem cells are affected by the interactions of extrinsic signals produced by components of the microenvironment niche, in addition to the chemical and physical properties of the extracellular matrix. Therefore, this study was initiated to assess the interaction of these cells on a synthetic nanofibrillar extracellular matrix that mimicked the geometry and nanotopography of the basement membrane for cellular growth. Methods This study has used a variety of experimental approaches to investigate the interaction of mouse neonatalderived spermatogonial stem-like cells on a synthetic random oriented three-dimensional nanofibrillar matrix composed of electrospun polyamide nanofibers (Ultra-Web™).Results Spermatogonial stem-like cell colonies were characterized by their ability to express α6-integrin, Thy-1, PLZF, and β1-integrin. After culture of cells on the nanofibrillar surfaces for 7 days, the number of colonies, the number of cells in each colony, and the average area of colonies were increased (P<0.05). However, the expression difference of related markers in both groups was not significant. A significantly higher proliferation and survival was observed in the nanofibrillar group (P<0.05). After transplantation into the testes of busulfan-treated adult mice, spermatogonial stem-like cell colonies that were cultured on the nanofibrillar surface demonstrated functionality, as verified by their ability to migrate to the seminiferous basal membrane, where they produced additional colonies. Conclusions These results have suggested that electrospun nanofibrillar surfaces could provide a more favorable microenvironment for in vitro short term culture of spermatogonial stem-like cell colonies.

show abstract

Spermatogonial Stem Cells

Cited by 165 publications

References 47 publications

GABA exists as a negative regulator of cell proliferation in spermaogonial stem cells

GABA exists as a negative regulator of cell proliferation in spermaogonial stem cells

Glial Cell Line-derived Neurotrophic Factor Regulation of Genes Essential for Self-renewal of Mouse Spermatogonial Stem Cells Is Dependent on Src Family Kinase Signaling

Behavior of mouse spermatogonial stem-like cells on an electrospun nanofibrillar matrix

Contact Info

Product

Resources

About