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LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment.

ABSTRACT: Spermatonial stem cells (SSCs) are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF), secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in vitro; these included 21,929 known lncRNAs from NONCODE library (version 3.0) and 33,975 predicted lncRNAs which were identified using Coding Potential Calculator. Analyses of these data should provide new insights into regulated mechanism in SSC self-renewal and proliferation. The data have been deposited in the Gene Expression Omnibus (series GSE66998).

SUBMITTER: Li L

PROVIDER: S-EPMC4583672 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment.

Li Lufan L Wang Min M Wang Mei M Wu Xiaoxi X Geng Lei L Xue Yuanyuan Y Wei Xiang X Jia Yuanyuan Y Wu Xin X

Genomics data 20150614

Spermatonial stem cells (SSCs) are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF), secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in vitr ...[more]

PMID: 26484267

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LncRNA Sequencing Analysis of Mouse spermatogonial stem cells during Glial cell-derived neurotrophic factor?GDNF?treatment

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LncRNA Sequencing Analysis of Mouse spermatogonial stem cells during Glial cell-derived neurotrophic factor（GDNF）treatment

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Transcription profiling of rat spermatogonial stem cells in presence and absence of GDNF (Glial cell derived neurotrophic factor)

Project description:Expression of GDNF-regulated genes was studied in cultures of self-renewing rat spermatogonial stem cells established from 8-10 day old rat pups maintained in a defined serum free medium. GDNF is the primary regulator of spermatogonial stem cell self renewal in the rat. GDNF regulated genes were identified using microarray profiling rat spermatogonial stem cells in the presence and absence of GDNF. Experiment Overall Design: Highly enriched population of rat spermatogonial stem cells were maintained in defined serum free media which allowed for their continued self-renewal in the presence of GDNF. GDNF was withdrawn from cultures for 18 hours followed by replacement for 2, 4, and 8 hours. Gene expression was studied using microarray profiling prior to GDNF withdrawal, after GDNF withdrawal, and after 2, 4, and 8 hours of GDNF replacement. 3 replicate samples from each timepoint were analyzed.

2009-04-18 | E-GEOD-15652 | biostudies-arrayexpress

Extended Treatment with Glial Cell Line-Derived Neurotrophic Factor in Parkinson's Disease.

Project description:BACKGROUND:Intraputamenal glial cell line-derived neurotrophic factor (GDNF), administered every 4 weeks to patients with moderately advanced Parkinson's disease, did not show significant clinical improvements against placebo at 40 weeks, although it significantly increased [18F]DOPA uptake throughout the entire putamen. OBJECTIVE:This open-label extension study explored the effects of continued (prior GDNF patients) or new (prior placebo patients) exposure to GDNF for another 40 weeks. METHODS:Using the infusion protocol of the parent study, all patients received GDNF without disclosing prior treatment allocations (GDNF or placebo). The primary outcome was the percentage change from baseline to Week 80 in the OFF state Unified Parkinson's Disease Rating Scale (UPDRS) motor score. RESULTS:All 41 parent study participants were enrolled. The primary outcome decreased by 26.7±20.7% in patients on GDNF for 80 weeks (GDNF/GDNF; N = 21) and 27.6±23.6% in patients on placebo for 40 weeks followed by GDNF for 40 weeks (placebo/GDNF, N = 20; least squares mean difference: 0.4%, 95% CI: -13.9, 14.6, p = 0.96). Secondary endpoints did not show significant differences between the groups at Week 80 either. Prespecified comparisons between GDNF/GDNF at Week 80 and placebo/GDNF at Week 40 showed significant differences for mean OFF state UPDRS motor (-9.6±6.7 vs. -3.8±4.2 points, p = 0.0108) and activities of daily living score (-6.9±5.5 vs. -1.0±3.7 points, p = 0.0003). No treatment-emergent safety concerns were identified. CONCLUSIONS:The aggregate study results, from the parent and open-label extension suggest that future testing with GDNF will likely require an 80- rather than a 40-week randomized treatment period and/or a higher dose.

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The Glial Cell-Derived Neurotrophic Factor (GDNF)-responsive Phosphoprotein Landscape Identifies Raptor Phosphorylation Required for Spermatogonial Progenitor Cell Proliferation.

Project description:Cytokine-dependent renewal of stem cells is a fundamental requisite for tissue homeostasis and regeneration. Spermatogonial progenitor cells (SPCs) including stem cells support life-long spermatogenesis and male fertility, but pivotal phosphorylation events that regulate fate decisions in SPCs remain unresolved. Here, we described a quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of SPCs following sustained stimulation with glial cell-derived neurotrophic factor (GDNF), an extrinsic factor supporting SPC proliferation. Stimulated SPCs contained 3382 identified phosphorylated proteins and 12141 phosphorylation sites. Of them, 325 differentially phosphorylated proteins and 570 phosphorylation sites triggered by GDNF were highly enriched for ERK1/2, GSK3, CDK1, and CDK5 phosphorylating motifs. We validated that inhibition of GDNF/ERK1/2-signaling impaired SPC proliferation and increased G2/M cell cycle arrest. Significantly, we found that proliferation of SPCs requires phosphorylation of the mTORC1 component Raptor at Ser863 Tissue-specific deletion of Raptor in mouse germline cells results in impaired spermatogenesis and progressive loss of spermatogonia, but in vitro increased phosphorylation of Raptor by raptor over-expression in SPCs induced a more rapidly growth of SPCs in culture. These findings implicate previously undescribed signaling networks in governing fate decision of SPCs, which is essential for the understanding of spermatogenesis and of potential consequences of pathogenic insult for male infertility.

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