Developmentally regulated lncRNAs expression in male germline
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE46896 | GEO | 2013/06/30
SECONDARY ACCESSION(S): PRJNA202978
REPOSITORIES: GEO
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Project description:To decipher the roles of non-coding RNAs during male germline development, we use the lncRNAs microarray to profile the genome-wide lncRNAs expression pattern in the male germline Testes samples from 6 time points were collected for lncRNAs and mRNAs microarray profiling
2013-06-30 | E-GEOD-46896 | biostudies-arrayexpress
Project description:Male and female germline stem cells are critical for passing genetic information from generation to generation. Accumulating evidences indicate that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) play important roles in self-renewal and differentiation of germline stem cells. However, the mechanisms remain largely unknown. In this study, we explored the mRNAs, lncRNAs and circRNAs expression profiles of male and female germline stem cells through high-throughput sequencing.
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Project description:In mammals, the transcriptome of large noncoding RNAs (lncRNAs) is believed to be greater than that of messenger RNAs (mRNAs). Some lncRNAs, especially large intergenic noncoding RNAs (lincRNAs), participate in epigenetic regulation by binding chromatin-modifying protein complexes and regulating protein-coding gene expression. Given that epigenetic regulation plays a critical role in male germline development, we embarked on expression profiling of both lncRNAs and mRNAs during male germline reprogramming and postnatal development using microarray analyses. We identified thousands of lncRNAs and hundreds of lincRNAs that are either up- or downregulated at six critical time points during male germ cell development. In addition, highly regulated lncRNAs were correlated with nearby (<30 kb) mRNA gene clusters, which were also significantly up- or downregulated. Large ncRNAs can be localized to both the nucleus and cytoplasm, with nuclear lncRNAs mostly associated with key components of the chromatin-remodeling protein complexes. Our data indicate that expression of lncRNAs is dynamically regulated during male germline development and that lncRNAs may function to regulate gene expression at both transcriptional and posttranscriptional levels via genetic and epigenetic mechanisms.
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Project description:Gametogenesis is dependent on the expression of germline-specific genes. However, it remains unknown how the germline epigenome is distinctly established from that of somatic lineages. Here we show that genes commonly expressed in somatic lineages and spermatogenesis-progenitor cells undergo repression in a genome-wide manner in late stages of the male germline and identify underlying mechanisms. SCML2, a germline-specific subunit of a Polycomb repressive complex 1 (PRC1), establishes the unique epigenome of the male germline through two distinct antithetical mechanisms. SCML2 works with PRC1 and promotes RNF2-dependent ubiquitination of H2A, thereby marking somatic/progenitor genes on autosomes for repression. Paradoxically, SCML2 also prevents RNF2-dependent ubiquitination of H2A on sex chromosomes during meiosis, thereby enabling unique epigenetic programming of sex chromosomes for male reproduction. Our results reveal divergent mechanisms involving a shared regulator by which the male germline epigenome is distinguished from that of the soma and progenitor cells.
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Project description:This study aims to investigate whether the passage of human chromosome 21 through the mouse male germline results in changes in the transcriptional deployment of the exogenous chromosome in the offspring generation. We used the Tc1 mouse model that stably carries almost an entire copy of human chromosome 21 and profiled the genome-wide pattern of non-methylated DNA using BioCAP-sequencing (doi: 10.1093/nar/gkr1207) in the livers of male- and female-germline derived Tc1 mice. This dataset contains only the samples for male-germline derived animals, BioCAP-Seq data for female-germline derived animals have already been deposited in Gene Expression Omnibus with the accession number GSE72208.
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Project description:This study aims to investigate whether the passage of human chromosome 21 through the mouse male germline results in changes in the transcriptional deployment of the exogenous chromosome in the offspring generation. We used the Tc1 mouse model that stably carries almost an entire copy of human chromosome 21 and profiled the genome-wide pattern of H3K4me3, H3K27ac, CEBPA, HNF4A and RNA polymerase II in liver tissue of male and female-germline derived Tc1 mice using ChIP-Seq. Furthermore, the genome-wide pattern of H3K4me3 was profiled in additional tissues including kidney, liver and brain.
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Project description:Germline development provides the founding cells for spermatogenesis and oogenesis in males and females, respectively. Disrupted germline differentiation or compromised testis development can lead to subfertility or infertility and are strongly associated with testis cancer in humans. In mice, SRY and SOX9 induce expression of a range of genes, including Fgf9, that promote Sertoli cell differentiation and testis development. FGF9 is also thought to promote male germline differentiation but the pathway through which it signals is unknown. As FGFs signal through Mitogen-Activated Protein Kinases (MAPKs) in other tissues, we explored whether FGF9 regulates male germline development through MAPK by inhibiting either FGF or MEK1/2 signalling in fetal testis cultures from embryonic day (E)12.5, immediately after gonadal sex determination and testis cord formation, but prior to male germline commitment. Inhibition of MEK1/2 disrupted mitotic arrest, dysregulated a broad range of male germline development genes and prevented the upregulation of key male germline markers DPPA4 and DNMT3L. In contrast, when FGF signalling was inhibited, the male germline specific transcriptional program and the expression of male germline markers DPPA4 and DNMT3L were unaffected, and the germ cells entered mitotic arrest normally. While male germline development was not disrupted by FGF inhibition, a significant number of genes were commonly altered after 24h of FGF or MEK1/2 inhibition including genes involved in maintenance germline stem cells, Nodal signalling, proliferation, and germline cancer. Together, these data demonstrate a novel and essential role for MEK1/2 signalling in male germline differentiation, but a surprisingly limited role for FGF signalling. Our data strongly indicate that additional ligands act through MEK1/2 to promote male germline differentiation and highlight a need for further mechanistic understanding of male germline development.
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Project description:Germline development provides the founding cells for spermatogenesis and oogenesis in males and females, respectively. Disrupted germline differentiation or compromised testis development can lead to subfertility or infertility and are strongly associated with testis cancer in humans. In mice, SRY and SOX9 induce expression of a range of genes, including Fgf9, that promote Sertoli cell differentiation and testis development. FGF9 is also thought to promote male germline differentiation but the pathway through which it signals is unknown. As FGFs signal through Mitogen-Activated Protein Kinases (MAPKs) in other tissues, we explored whether FGF9 regulates male germline development through MAPK by inhibiting either FGF or MEK1/2 signalling in fetal testis cultures from embryonic day (E)12.5, immediately after gonadal sex determination and testis cord formation, but prior to male germline commitment. Inhibition of MEK1/2 disrupted mitotic arrest, dysregulated a broad range of male germline development genes and prevented the upregulation of key male germline markers DPPA4 and DNMT3L. In contrast, when FGF signalling was inhibited, the male germline specific transcriptional program and the expression of male germline markers DPPA4 and DNMT3L were unaffected, and the germ cells entered mitotic arrest normally. While male germline development was not disrupted by FGF inhibition, a significant number of genes were commonly altered after 24h of FGF or MEK1/2 inhibition including genes involved in maintenance germline stem cells, Nodal signalling, proliferation, and germline cancer. Together, these data demonstrate a novel and essential role for MEK1/2 signalling in male germline differentiation, but a surprisingly limited role for FGF signalling. Our data strongly indicate that additional ligands act through MEK1/2 to promote male germline differentiation and highlight a need for further mechanistic understanding of male germline development.
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Project description:Using high-throughput sequencing, we probed the H3K4me2 and H3K4me3 landscape in the bam mutant testes which are enriched with earlier stages of male germline.
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Project description:Pheromones exchanged by conspecifics are a major class of chemical signals that can alter behavior, physiology, and development. In particular, males and females communicate with potential mating partners via sex pheromones to promote reproductive success. Physiological and developmental mechanisms by which pheromones facilitate progeny production remain largely enigmatic. Here we describe how a C. elegans male pheromone, ascr#10, improves the oogenic germline. Before most signs of aging become evident, C. elegans hermaphrodites start producing lower quality gametes characterized by abnormal morphology, increased rates of chromosomal nondisjunction, and higher penetrance of deleterious alleles. We show that exposure to the male pheromone substantially ameliorates all of these defects and reduces embryonic lethality. ascr#10 stimulates proliferation of germline precursor cells in adult hermaphrodites. Greater precursor supply increases physiological germline cell death, which is required to improve oocyte quality in older mothers. The hermaphrodite germline is sensitive to the pheromone only during a time window, comparable in duration to a larval stage, used by the pre-reproductive adults to assess suitability of the environment for reproduction. Our results identify developmental events that occur in the oogenic germline in response to a male pheromone. They also suggest that the opposite effects of the pheromone on gamete quality and organismal longevity arise from a competition over resource allocation between soma and the germline.
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