Single-cell Definition of the full-term Developmental Program of Male Mouse Germline
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ABSTRACT:
PROVIDER: PRJNA622922 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11475400_1.fastq.gz | Fastqsanger.gz | |||
| SRR11475400_2.fastq.gz | Fastqsanger.gz | |||
| SRR11475401_1.fastq.gz | Fastqsanger.gz | |||
| SRR11475401_2.fastq.gz | Fastqsanger.gz | |||
| SRR11475402_1.fastq.gz | Fastqsanger.gz |
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Project description:Germ cells are essential for the genetic information transition to subsequent generations of the species relying on sexual reproduction. Full-term developmental trajectory of germ cells provides a paradigm for understanding mammalian germline and germline niches with pivotal knowledge from tremendous in vivo and in vitro studies on the critical role of master regulators in regulating the initiation and maintenance of germline.To characterise the dynamic process of transcriptional programme underlying male mouse germline development, we generated single-cell RNA sequencing profiles for 28 developmental time-points from dissected early embryos or male gonads that were collected between embryonic day (E) 6.5 and postnatal day (P) 8 at one-day intervals, P10-P14 at two-day intervals and at juvenile stage of P30 and P35 as well as adult (8-10 weeks).
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Project description:Spermatogenesis is a unidirectional differentiation process to produce haploid sperm. However, it remains largely unknown how the gene expression program is determined to direct a unidirectional differentiation. Here we unveil the high-resolution 3D chromatin architecture of male germ cells and show that CTCF-mediated 3D chromatin predetermines the gene expression program required for spermatogenesis. At the mitosis-to-meiosis transition, the germline-specific Polycomb protein SCML2 resolves chromatin loops specific to mitotic spermatogonia. On autosomes, CTCF-mediated 3D chromatin manifests the structural feature of meiosis-specific super-enhancer (meiotic SE) loci already in undifferentiated spermatogonia. In meiotic spermatocytes, the master transcription factor A-MYB is recruited to these meiotic SE loci to strengthen their 3D contacts to instruct the burst of meiotic gene expression. Further, SCML2 and A-MYB establish unique 3D chromatin of the sex chromosomes in meiotic sex chromosome inactivation. We propose that CTCF-mediated 3D chromatin underlines epigenetic priming to direct unidirectional differentiation, thereby determining the cellular identity of the male germline.
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Project description:Spermatogenesis is a unidirectional differentiation process to produce haploid sperm. However, it remains largely unknown how the gene expression program is determined to direct a unidirectional differentiation. Here we unveil the high-resolution 3D chromatin architecture of male germ cells and show that CTCF-mediated 3D chromatin predetermines the gene expression program required for spermatogenesis. At the mitosis-to-meiosis transition, the germline-specific Polycomb protein SCML2 resolves chromatin loops specific to mitotic spermatogonia. On autosomes, CTCF-mediated 3D chromatin manifests the structural feature of meiosis-specific super-enhancer (meiotic SE) loci already in undifferentiated spermatogonia. In meiotic spermatocytes, the master transcription factor A-MYB is recruited to these meiotic SE loci to strengthen their 3D contacts to instruct the burst of meiotic gene expression. Further, SCML2 and A-MYB establish unique 3D chromatin of the sex chromosomes in meiotic sex chromosome inactivation. We propose that CTCF-mediated 3D chromatin underlines epigenetic priming to direct unidirectional differentiation, thereby determining the cellular identity of the male germline.
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Project description:Spermatogenesis is a unidirectional differentiation process that generates haploid sperm, but how the gene expression program that directs this process is established is largely unknown. Here we determine the high-resolution 3D chromatin architecture of male germ cells during spermatogenesis and show that CTCF-mediated 3D chromatin predetermines the gene expression program required for spermatogenesis. In undifferentiated spermatogonia, CTCF-mediated chromatin interactions between meiosis-specific super-enhancers (SE) loci and target genes precede activation of meiosis-specific SEs on autosomes. These meiotic SE recruit the master transcription factor A-MYB in meiotic spermatocytes, which strengthens their 3D contacts and instructs a burst of meiotic gene expression. We also find that at the mitosis-to-meiosis transition, the germline-specific Polycomb protein SCML2 resolves chromatin loops that are specific to mitotic spermatogonia. Moreover, SCML2 and A-MYB establish the unique 3D chromatin organization of sex chromosomes during meiotic sex chromosome inactivation. We propose that CTCF-mediated 3D chromatin organization enforces epigenetic priming that directs unidirectional differentiation, thereby determining the cellular identity of the male germline.
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Project description:CTCF-mediated 3D chromatin predetermines the gene expression program in the male germline
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Project description:CTCF-mediated 3D chromatin predetermines the gene expression program in the male germline (RNA-Seq)
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Project description:CTCF-mediated 3D chromatin predetermines the gene expression program in the male germline (ChIP-seq)
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Project description:CTCF-mediated 3D chromatin predetermines the gene expression program in the male germline (Hi-C)
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Project description:Spermatogenesis in the Drosophila male germline proceeds through a unique transcriptional program controlled both by germline-specific transcription factors and by testis-specific versions of core transcriptional machinery. This program includes the activation of genes on the heterochromatic Y chromosome, and reduced transcription from the X chromosome, but how expression from these sex chromosomes is regulated has not been defined. To resolve this, we profiled active chromatin features in the testes from wildtype and meiotic arrest mutants and integrate this with single-cell gene expression data from the Fly Cell Atlas. These data assign the timing of promoter activation for genes with germline-enriched expression throughout spermatogenesis, and general alterations of promoter regulation in germline cells. By profiling both active RNA polymerase II and histone modifications in isolated spermatocytes, we detail widespread patterns associated with regulation of the sex chromosomes. Our results demonstrate that the X chromosome is not enriched for silencing histone modifications, implying that sex chromosome inactivation does not occur in Drosophila. Instead, a lack of dosage compensation in spermatocytes accounts for the reduced expression from this chromosome. Finally, profiling uncovers dramatic ubiquitinylation of histone H2A and lysine-16 acetylation of histone H4 across the Y chromosome in spermatocytes that may contribute to the activation of this heterochromatic chromosome.
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