DAZL mediates a broad translational program regulating expansion and differentiation of spermatogonial progenitors
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA606263 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11040400.fastq.gz | Fastqsanger.gz | |||
| SRR11040401.fastq.gz | Fastqsanger.gz | |||
| SRR11040402.fastq.gz | Fastqsanger.gz | |||
| SRR11040403.fastq.gz | Fastqsanger.gz | |||
| SRR11040378.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Fertility across metazoa requires the germline-specific DAZ family of RNA-binding proteins. Here we examine whether DAZL directly regulates progenitor spermatogonia using a conditional genetic mouse model and in vivo biochemical approaches combined with chemical synchronization of spermatogenesis. We find that the absence of Dazl impairs both expansion and differentiation of the spermatogonial progenitor population. In undifferentiated spermatogonia, DAZL binds the 3' UTRs of ~2,500 protein-coding genes. Some targets are known regulators of spermatogonial proliferation and differentiation while others are broadly expressed, dosage-sensitive factors that control transcription and RNA metabolism. DAZL binds 3' UTR sites conserved across vertebrates at a UGUU(U/A) motif. By assessing ribosome occupancy in undifferentiated spermatogonia, we find that DAZL increases translation of its targets. In total, DAZL orchestrates a broad translational program that amplifies protein levels of key spermatogonial and gene regulatory factors to promote the expansion and differentiation of progenitor spermatogonia.
| S-EPMC7445011 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-07-22 | GSE145177 | GEO
Project description:Purpose: The goals of this study are to clarify influence of long-term expansion on the spermatogenesis potential of tree shrew spermatogonial stem cells （SSCs）
2023-04-06 | GSE228744 | GEO
Project description:Maintenance and self-renewal of the spermatogonial stem cell (SSC) population is the cornerstone of male fertility. In this manuscript we have identified a key role for the nucleosome remodelling protein Chromodomain Helicase DNA binding protein 4 (CHD4) in regulating SSC function. Gene expression analyses revealed that CHD4 expression is largely restricted to spermatogonia in the mouse testis, and is particularly enriched in SSCs. Using spermatogonial transplantation techniques and RNAi mediated knockdown it was established that loss of Chd4 expression significantly impairs SSC regenerative capacity, resulting in a ~50% reduction in colonisation of recipient testes. A single cell RNA-seq comparison depicted reduced expression of ‘self-renewal’ genes such as Gfra1 and Pten following Chd4 knockdown, along with increased expression of signature progenitor genes, Neurog3 and Dazl. Co-immunoprecipitation analyses demonstrated that CHD4 regulates gene expression in spermatogonia not only though its traditional association with the remodelling complex NuRD, but also via interaction with the GDNF-responsive transcription factor SALL4. Cumulatively, the results of this study depict a previously unappreciated fundamental role for CHD4 in controlling fate decisions in the spermatogonial pool.
2021-06-17 | PXD022066 | Pride
Project description:The RNA binding protein Dazl is essential for gametogenesis, but its direct in vivo functions, RNA targets, and the molecular basis for germ cell loss in DAZL null mice are unknown. Here, we mapped transcriptome-wide Dazl-RNA interactions in vivo, revealing Dazl binding to thousands of mRNAs via polyA-proximal 3’UTR interactions. In parallel, fluorescence activated cell sorting and RNA-Seq identified mRNAs sensitive to Dazl deletion in male germ cells. Despite binding a broad set of mRNAs, integrative analyses indicate that Dazl post-transcriptionally controls only a subset of its mRNA targets, namely those corresponding to a network of genes critical for germ cell proliferation and survival. Additionally, we provide evidence that polyA sequences have key roles in specifying Dazl-RNA interactions across the transcriptome. Altogether, our results reveal a mechanism for Dazl-RNA binding, and illustrate that Dazl functions as a master regulator of a post-transcriptional mRNA program essential for germ cell survival.
2018-09-18 | GSE120098 | GEO
Project description:The RNA binding protein Dazl is essential for gametogenesis, but its direct in vivo functions, RNA targets, and the molecular basis for germ cell loss in DAZL null mice are unknown. Here, we mapped transcriptome-wide Dazl-RNA interactions in vivo, revealing Dazl binding to thousands of mRNAs via polyA-proximal 3?UTR interactions. In parallel, fluorescence activated cell sorting and RNA-Seq identified mRNAs sensitive to Dazl deletion in male germ cells. Despite binding a broad set of mRNAs, integrative analyses indicate that Dazl post-transcriptionally controls only a subset of its mRNA targets, namely those corresponding to a network of genes critical for germ cell proliferation and survival. Additionally, we provide evidence that polyA sequences have key roles in specifying Dazl-RNA interactions across the transcriptome. Altogether, our results reveal a mechanism for Dazl-RNA binding, and illustrate that Dazl functions as a master regulator of a post-transcriptional mRNA program essential for germ cell survival.
2018-09-18 | GSE120097 | GEO
Project description:In mouse embryos, sex-specific differentiation of primordial germ cells (PGCs) begins with distinct cell cycle regulations: while PGCs in female (XX) gonads enter meiosis, PGCs in male (XY) gonads defer meiosis and arrest cell cycle1,2. The mitotic quiescence in XY gonads requires Nanos2, an evolutionarily conserved RNA-binding protein implicated in RNA degradation3-5; however, underlying mechanisms including the identity of its target mRNAs in vivo remain unknown. Here we show that Nanos2 negatively regulates Dazl (Deleted in azoospermia-like), a germline-specific gene encoding an RNA-binding protein that is implicated in translational control and meiotic initiation6,7. Comprehensive microarray analyses identified Dazl as one of the genes that were up-regulated in Nanos2-deficient XY gonads, but down-regulated in Nanos2-expressing XX gonads. Analysis of a BAC transgenic mouse line, in which the 3’UTR of Dazl can be removed by Flp-Frt recombination system, showed that repression of Dazl is likely achieved by the association of Nanos2 with Dazl’s 3’UTR. Elevated levels of Dazl expression in the transgenic XY PGCs resulted in abnormal progression of cell cycles including meiosis, reminiscent of the phenotype observed in Nanos2-/- XY gonads. This phenotype was suppressed by inhibiting retinoic acid (RA) signaling, suggesting that Nanos2 represses Dazl to prevent RA-induced cell cycle progression in XY PGCs. Furthermore, we show that a part of Nanos2-associated mRNAs, most of which are up-regulated in Nanos2-/- XY gonads, can also associate with Dazl, and that excess Dazl impedes localization of Nanos2 to processing-bodies where RNA degradation takes place, suggesting that repression of Dazl is required for Nanos2 to efficiently degrade its target mRNAs. These data provide the first link between the two RNA-binding proteins that play pivotal roles in sexual differentiation of murine PGCs.
2015-12-01 | GSE56794 | GEO
Project description:In mouse embryos, sex-specific differentiation of primordial germ cells (PGCs) begins with distinct cell cycle regulations: while PGCs in female (XX) gonads enter meiosis, PGCs in male (XY) gonads defer meiosis and arrest cell cycle1,2. The mitotic quiescence in XY gonads requires Nanos2, an evolutionarily conserved RNA-binding protein implicated in RNA degradation3-5; however, underlying mechanisms including the identity of its target mRNAs in vivo remain unknown. Here we show that Nanos2 negatively regulates Dazl (Deleted in azoospermia-like), a germline-specific gene encoding an RNA-binding protein that is implicated in translational control and meiotic initiation6,7. Comprehensive microarray analyses identified Dazl as one of the genes that were up-regulated in Nanos2-deficient XY gonads, but down-regulated in Nanos2-expressing XX gonads. Analysis of a BAC transgenic mouse line, in which the 3’UTR of Dazl can be removed by Flp-Frt recombination system, showed that repression of Dazl is likely achieved by the association of Nanos2 with Dazl’s 3’UTR. Elevated levels of Dazl expression in the transgenic XY PGCs resulted in abnormal progression of cell cycles including meiosis, reminiscent of the phenotype observed in Nanos2-/- XY gonads. This phenotype was suppressed by inhibiting retinoic acid (RA) signaling, suggesting that Nanos2 represses Dazl to prevent RA-induced cell cycle progression in XY PGCs. Furthermore, we show that a part of Nanos2-associated mRNAs, most of which are up-regulated in Nanos2-/- XY gonads, can also associate with Dazl, and that excess Dazl impedes localization of Nanos2 to processing-bodies where RNA degradation takes place, suggesting that repression of Dazl is required for Nanos2 to efficiently degrade its target mRNAs. These data provide the first link between the two RNA-binding proteins that play pivotal roles in sexual differentiation of murine PGCs.
2015-12-01 | GSE56793 | GEO
Project description:The autosomal gene Dazl is a member of highly conservative DAZ family, all of which contains a RNA binding domain and expresses in germ cells. In mice, Dazl plays an essential role in germ cell development, germ cell lost in Dazl knockout mouse on pure C57BL/6 strain background. Here we use HITS-CLIP to globally characterize the genome-wide target RNA of Dazl in mouse testes. Sequencing data provides large quantities of clues to help us to get close to the truth of Dazl function. We find over 1700 RNAs are bind by Dazl mainly at 3’UTR and the genes associated with transcription, RNA splicing and reproductive cellular process are enriched significantly.
2019-10-09 | GSE113710 | GEO
Project description:We developed a method to identify chromatin-associated proteins by mass spectrometry. In addition to many known DNA and chromatin-binders, we identified several RNA-binding proteins in the chromatin composition of mouse embryonic stem cells (mESC). Interestingly, we found Dazl as a RBP that specifically binds to chromatin in mESC grown in 2iL condition. So far, Dazl was reported as a RBP that regulates the stability of transcripts in cytoplasm. To identify the binding sites of Dazl on the genome, we carried out a ChIP-seq experiment. As a result, we detected about 1300 reproducible Dazl ChIP-seq peaks. Interestingly, most of the peaks are located close to the transcription start sites of developmental and pluripotency-related genes.
2020-12-25 | E-MTAB-9302 | biostudies-arrayexpress