Functional Differences between GDNF-Dependent and FGF2-Dependent Mouse Spermatogonial Stem Cell Self-Renewal

Takashima, Seiji; Kanatsu-Shinohara, Mito; Tanaka, Takashi; Morimoto, Hiroko; Inoue, Kimiko; Ogonuki, Narumi; Jijiwa, Mayumi; Takahashi, Masahide; Ogura, Atsuo; Shinohara, Takashi

doi:10.1016/j.stemcr.2015.01.010

Cited by 143 publications

(122 citation statements)

References 40 publications

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“…In previous studies, we found that ID4-EGFP + spermatogonia are also GFRA1 + (Chan et al, 2014). In the current study, our transcriptome analyses demonstrate that Gfra1 expression is significantly upregulated in ID4-EGFP Bright SSCs; and a previous study found that levels of GFRA1 are positively associated with colonization activity in a transplantation assay (Takashima et al, 2015), although the potency is considerably less than that of the ID4-EGFP Bright population. Thus, it is likely that spermatogonia expressing high levels of GFRA1 are the true SSCs and those with lower levels are immediate progenitors.…”

Section: Discussionsupporting

confidence: 68%

ID4 levels dictate the stem cell state in mouse spermatogonia

et al. 2017

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Spermatogenesis is a classic model of cycling cell lineages that depend on a balance between stem cell self-renewal for continuity and the formation of progenitors as the initial step in the production of differentiated cells. The mechanisms that guide the continuum of spermatogonial stem cell (SSC) to progenitor spermatogonial transition and precise identifiers of subtypes in the process are undefined. Here we used an Id4-eGfp reporter mouse to discover that EGFP intensity is predictive of the subsets, with the ID4-EGFP Bright population being mostly, if not purely, SSCs, whereas the ID4-EGFP Dim population is in transition to the progenitor state. These subsets are also distinguishable by transcriptome signatures. Moreover, using a conditional overexpression mouse model, we found that transition from the stem cell to the immediate progenitor state requires downregulation of Id4 coincident with a major change in the transcriptome. Collectively, our results demonstrate that the level of ID4 is predictive of stem cell or progenitor capacity in spermatogonia and dictates the interface of transition between the different functional states.

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Section: Discussionsupporting

confidence: 68%

ID4 levels dictate the stem cell state in mouse spermatogonia

et al. 2017

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“…GDNF can activate the PI3K/AKT pathway by binding to the GDNF receptor components GFRA1 and RET to stimulate SSC/SPC proliferation (Lee et al 2007, Oatley et al 2007). FGF2 can also significantly increase SSC/ SPC proliferation (Ishii et al 2012), whereas the balance between the FGF2 and GDNF levels mediates SSC selfrenewal, as an increased level of GDNF associated with an elevated stem cell number is observed in FGF2-depleted testes (Takashima et al 2015). In addition to stimulating self-renewal, Sertoli cells are the main source of RA in mouse testes.…”

Section: Extrinsic Stimulation and Ssc/spc-associated Microenvironmentsmentioning

confidence: 99%

“…Comparing to prospermatogonia, postnatal SSC/SPCs are more heterogeneous, even within subpopulations with identical surface markers, for instance GFRA1 C , PLZF C and THY1 C SSC/SPCs (Kubota et al 2003, Gassei & Orwig 2013, Hermann et al 2015, Takashima et al 2015. The differences in isolation protocols and the affinity of antibodies may have effects on the enrichments of subpopulations with specific cellular states (Buageaw et al 2005, Ebata et al 2005, Grisanti et al 2009, Hermann et al 2015, Takashima et al 2015, Vlachogiannis et al 2015.…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

“…The differences in isolation protocols and the affinity of antibodies may have effects on the enrichments of subpopulations with specific cellular states (Buageaw et al 2005, Ebata et al 2005, Grisanti et al 2009, Hermann et al 2015, Takashima et al 2015, Vlachogiannis et al 2015. In addition, a suitable 3D culture system of SSC/SPCs with living cell tracking and epigenome-wide single cell analysis without PCR amplification will lead to further understanding of SSC/SPC self-renewal and differentiation decisions.…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

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Epigenetic factors in the regulation of prospermatogonia and spermatogonial stem cells

Tseng¹,

Liao²,

Yu³

et al. 2015

Reproduction

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Appropriate regulation of epigenome within cells is crucial for the determination of cell fate and contributes to the lifelong maintenance of tissue homeostasis. Epigenomic re-establishment during embryonic prospermatogonia development and fine-tune of the epigenetic landscape in postnatal spermatogonial stem cells (SSCs) are two key processes required for functional male germ cell formation. Repression of re-activated transposons and male germline-specific epigenome establishment occur in prospermatogonia, whereas modulations of the epigenetic landscape is important for SSC self-renewal and differentiation to maintain the stem cell pool and support long-term sperm production. Here, we describe the impact of epigenome-related regulators and small non-coding RNAs as well as the influence of epigenome modifications that result from extrinsic signaling for controlling the decision between self-renewal, differentiation and survival in mouse prospermatogonia and SSCs. This article provides a review of epigenome-related molecules involved in cell fate determination in male germ cells and discusses the intriguing questions that arise from these studies.Reproduction (2015) 150 R77-R91

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“…In mice and human, SSCs self-renewal is stimulated by Glial cell lineDerived Neurotrophic Factor (GDNF) through the sertoli cells, and Fibroblast Growth Factor 2 (FGF2) is expressed in Leydig cells which interacts with GDNF to enhance proliferation rate of SSCs [39]. According to previous reports, around 50% of the SSCs populations endured selfrenewal through GDNF, whereas reaming 50% will further differentiate into spermatogonia to continue production of spermatozoa through FGF2 and GDNF interaction [52,53]. In addition the controlling of the endocrine and local signaling system, some miRNAs are also involved in regulation and differentiation of .…”

Section: Micrornas and Spermatogonial Stem Cellsmentioning

confidence: 99%

Review: Role of microRNAs during spermatogenesis in mammals

Shah¹

2018

PAB

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The spermatogenesis in mammals comprises three stages: the mitotic proliferation of spermatogonia, meiosis of spermatocyte, which produces haploid spermatids, and spermiogenesis which leads spermatozoa into the tubule lumen. Each step of spermatogenesis is controlled by a number of factors including microRNAs (miRNAs) for the regulation of gene expression, these single-stranded non-coding small RNAs molecules contains about 19~25 nucleotides. Since first miRNAs (Let-7 and lin-4) were discovered in Caenorhabditis elegance, thousands of miRNA have been identified from different species in the past 23 years. It has been reported that the miRNAs function as guide molecules in post-transcriptional regulation by base pairing with target messenger RNA (mRNA) and lead to cleavage or translational repression. Recently, several pieces of evidence suggested that the miRNAs are closely related to the spermatogenesis by the analyzing mRNA changes in testicular tissue from different animal species. The present review has summarized the recent progress on the role of miRNAs during spermatogenesis which may contribute to understate the spermatogenic arrest in mammals.

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Functional Differences between GDNF-Dependent and FGF2-Dependent Mouse Spermatogonial Stem Cell Self-Renewal

Cited by 143 publications

References 40 publications

ID4 levels dictate the stem cell state in mouse spermatogonia

ID4 levels dictate the stem cell state in mouse spermatogonia

Epigenetic factors in the regulation of prospermatogonia and spermatogonial stem cells

Review: Role of microRNAs during spermatogenesis in mammals

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