Germ cell progression through zebrafish spermatogenesis declines with age
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PROVIDER: PRJNA1150539 | ENA |
REPOSITORIES: ENA
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Project description:Vertebrate spermatogonial stem cells maintain sperm production over the lifetime of an animal but fertility declines with age. While morphological studies have informed our understanding of typical spermatogenesis, the molecular and cellular mechanisms underlying the maintenance and decline of spermatogenesis are not yet understood. We used single-cell RNA sequencing to generate a developmental atlas of the aging zebrafish testis. All testes contained spermatogonia, but we observed a progressive decline in spermatogenesis that correlates with age. Testes from some older males only contained spermatogonia and a reduced population of spermatocytes. Spermatogonia in older males are transcriptionally distinct from spermatogonia in testes capable of robust spermatogenesis. Immune cells including macrophages and lymphocytes drastically increase in abundance in testes that cannot complete spermatogenesis. Our developmental atlas reveals the cellular changes as the testis ages and defines a molecular roadmap for the regulation of spermatogenesis.
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Project description:Foxo signaling declines with age
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Project description:Analysis of cell-specific expression patterns produced unique and characteristic groups of transcripts that provide greater insight into the activities, biological and chronological, of testicular cell types during the progression of spermatogenesis Experiment Overall Design: Four types of mouse germ cells
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Project description:Post-transcriptional regulation mediated by RNA binding proteins is crucial for male germline development. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), an RNA binding protein, is specifically expressed in human and mouse male gonads and is involved in manifold biological processes and tumorigenesis. However, the function of IGF2BP1 in mammalian spermatogenesis remains poorly understood. Herein, we generated an Igf2bp1 conditional knockout mouse model using Nanos3-Cre. Germ cell deficiency of Igf2bp1 in mice caused spermatogenic defects in an age-dependent manner, resulting in decreased numbers of undifferentiated spermatogonia and increased germ cell apoptosis. Immunoprecipitation-mass spectrometry analysis revealed that ELAV-like RNA binding protein 1, a well-recognized mRNA stabilizer, interacted with IGF2BP1. Single cell RNA-sequencing showed distinct mRNA profiles in spermatogonia from conditional knockout versus wide type mice. Further research showed that IGF2BP1 plays a vital role in the modulation of spermatogenesis by regulating Lin28a mRNA, which is essential for clonal expansion of undifferentiated spermatogonia. Thus, our results highlight the crucial effects of IGF2BP1 on spermatogonia for the long-term maintenance of spermatogenesis
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Project description:Male germ cell meiosis is essential for generating haploid spermatozoa in mice. Here, we investigate the essential role of DIS3 in male germ cell meiosis in mice. Conditional inactivation of DIS3 in spermatocytes with Stra8-cre transgenic mice have severely impaired meiotic progression, which results in defective meiosis and spermatogenesis. RNA-seq analysis reveals that Dis3 deficiency causes significant dysregulation of the expression of transcripts in mutant testes. Meiosis-associated genes are significantly decreased in the absence of DIS3. Therefore, we show that DIS3 ribonuclease plays a critical role in germ cell meiosis during spermatogenesis in mice.
2021-07-16 | GSE180197 | GEO
Project description:Temporal study of the first wave of spermatogenesis in juvenile mouse testis and analysis of four germ cell deficient mouse models.<br> A series of purified testis cell-types (McCarrey libraries)constituting a focussed gene set was exploited to examine gene expression in prepubertal mouse testis. Testis RNA from C57/BL6J mice at various ages post partum was compared to a common control consisting of adult (8 week) testis RNA from the same strain(also corresponding to the last time-point).This generates a time course showing the activation of genes on the array across the first wave of spermatogenesis, which can then be correlated with the appearance of specific germ cell types, allowing assignation of unknown genes to differing cell types. <br> <br> Adult testis RNA from four different genetic models of infertility (XXSxrb, mshi, Bax -/-, bs) were compared to age- and strain-matched normal control testis RNA. These models possess different cellular complements within the testis, which can be interpreted within the framework established by the first wave analysis and used to refine the assignment of genes to cell types.
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Project description:We applied ultra-low-input native ChIP-seq and profiled genome-wide H3K9me3 distribution in four germ cell types during spermatogenesis.
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Project description:Sertoli cells (SCs), the only somatic cells within seminiferous tubules, associate intimately with developing germ cells. They not only provide physical and nutritional support but also secrete factors essential to the complex developmental processes of germ cell proliferation and differentiation. The SC transcriptome must therefore adapt rapidly during the different stages of spermatogenesis. We report comprehensive genome-wide expression profiles of pure populations of SCs isolated at 5 distinct stages of the first wave of mouse spermatogenesis, using RNA sequencing technology. We were able to reconstruct about 13 901 high-confidence, nonredundant coding and noncoding transcripts, characterized by complex alternative splicing patterns with more than 45% comprising novel isoforms of known genes. Interestingly, roughly one-fifth (2939) of these genes exhibited a dynamic expression profile reflecting the evolving role of SCs during the progression of spermatogenesis, with stage-specific expression of genes involved in biological processes such as cell cycle regulation, metabolism and energy production, retinoic acid synthesis, and blood-testis barrier biogenesis. Finally, regulatory network analysis identified the transcription factors endothelial PAS domain-containing protein 1 (EPAS1/Hif2α), aryl hydrocarbon receptor nuclear translocator (ARNT/Hif1β), and signal transducer and activator of transcription 1 (STAT1) as potential master regulators driving the SC transcriptional program. Our results highlight the plastic transcriptional landscape of SCs during the progression of spermatogenesis and provide valuable resources to better understand SC function and spermatogenesis and its related disorders, such as male infertility. Genome-wide expression profiling analysis using Illumina next-generation sequencing technology
2015-08-25 | E-GEOD-59698 | biostudies-arrayexpress
Project description:WIN 18,446/RA treatment of neonatal mice was used to synchronize the initial wave of spermatogenesis and identify novel messages expressed within either germ or Sertoli cells as spermatogonia enter meiosis. germ cell-specific (Stra8-cre: RiboTag; or Ngn3-cre:RiboTag) and Sertoli cell-specific (Amh-Cre: RiboTag)
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