Oocyte piRNAs mediate intergenerational transmission of an acquired metabolic disorder (small RNA sequencing)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA730307 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14559671.fastq.gz | Fastqsanger.gz | |||
| SRR14559672.fastq.gz | Fastqsanger.gz | |||
| SRR14559673.fastq.gz | Fastqsanger.gz | |||
| SRR14559674.fastq.gz | Fastqsanger.gz | |||
| SRR14559675.fastq.gz | Fastqsanger.gz |
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Project description:Traditional research has focused on DNA as the molecule that carries heritable information from the parent to the offspring. However, increasing evidence suggests that information beyond the DNA sequence, termed epigenetic information, can also transmit certain information from one generation to the next. Whereas paternal epigenetic germline inheritance has been well elucidated, as the father contributes little more than a sperm cell to the offspring, maternal epigenetic inheritance via gametes remains largely unclear. Here, using an in vitro fertilization system and a micromanipulation strategy, we demonstrate that oocyte piRNAs mediate intergenerational transmission of an acquired metabolic disorder. Changes in the expression profiles of many oocyte piRNAs are observed in a maternal chronic high-fat diet (HFD) mouse model. Injection of the oocyte piRNAs from HFD females into normal zygotes resulted in impaired glucose tolerance and decreased insulin sensitivity in the F1 offspring. A series of genes involved in glucose metabolism and the insulin signaling pathway were differentially expressed in the pancreatic islets of the F1 offspring. Bisulfite genome sequencing of the islets of the F1 offspring revealed changes in cytosine methylation that correlated with the observed gene expression patterns. These data identified oocyte piRNAs as novel carriers of epigenetic information and highlight the importance of long-term maternal health before conception.
2021-05-17 | GSE174504 | GEO
Project description:Intergenerational metabolic priming by sperm piRNAs
| PRJNA722018 | ENA
Project description:Increasing evidences indicate diet-induced metabolic disorder could be paternally inherited, but the exact sperm epigenetic carrier remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we revealed that a highly enriched subset of sperm small RNAs (30-34 nt) that derived from the 5â halves of tRNAs (tsRNAs), exhibit changes in both expression profiles and RNA modifications. Injection of sperm tsRNAs from HFD male but not synthetic tsRNAs lacking RNA modifications, into normal zygotes generated metabolic disorders in the F1 offspring. Injection of HFD sperm tsRNAs derails gene expression in both early embryos and islets of F1 offspring, enriched in metabolic pathways, but unrelated to DNA methylation at CpG-enriched region. Collectively, we uncover sperm tsRNAs as a type of âepigenetic carrierâ that mediate intergenerational inheritance of acquired traits. Mature sperm small-RNA profiles between High-fat-diet (HFD) and Normal-diet (ND) males; Transcriptional profiles of 8-cell embryos and balstocysts that developed from zygotes that injected with sperm RNAs from HFD vs ND males. Transcriptional profiles and RRBS profiles of islets of F1 offsrping that generated from zygotes that injected with sperm RNAs from HFD vs ND males.
2015-12-31 | E-GEOD-75544 | biostudies-arrayexpress
Project description:Preconception parental environment can reproducibly program offspring phenotype without altering the DNA sequence, yet the mechanisms underpinning this ‘epigenetic inheritance’ remains elusive. Here, we demonstrate the existence of an intact piRNA-pathway in mature Drosophila sperm and show that pathway modulation alters offspring gene transcription in a sequence-specific manner. We map a dynamic small RNA content in developing sperm and find that the mature sperm carry a highly distinct small RNA cargo. By biochemical pulldown, we identify a small RNA subset bound directly to piwi protein. And, we show that piRNA-pathway controlled sperm small RNAs are linked to target gene repression in offspring. Critically, we find that full piRNA-pathway dosage is necessary for the intergenerational metabolic and transcriptional reprogramming events triggered by high paternal dietary sugar. These data provide a direct link between regulation of endogenous mature sperm small RNAs and transcriptional programming of complementary sequences in offspring. Thus, we identify a novel mediator of paternal intergenerational epigenetic inheritance.
2022-01-01 | GSE172107 | GEO
Project description:Increasing evidences indicate diet-induced metabolic disorder could be paternally inherited, but the exact sperm epigenetic carrier remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we revealed that a highly enriched subset of sperm small RNAs (30-34 nt) that derived from the 5’ halves of tRNAs (tsRNAs), exhibit changes in both expression profiles and RNA modifications. Injection of sperm tsRNAs from HFD male but not synthetic tsRNAs lacking RNA modifications, into normal zygotes generated metabolic disorders in the F1 offspring. Injection of HFD sperm tsRNAs derails gene expression in both early embryos and islets of F1 offspring, enriched in metabolic pathways, but unrelated to DNA methylation at CpG-enriched region. Collectively, we uncover sperm tsRNAs as a type of “epigenetic carrier” that mediate intergenerational inheritance of acquired traits.
2015-12-31 | GSE75544 | GEO
Project description:The discovery of RNAs (e.g. mRNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function in delivering additional paternal information aside from solely providing the DNA1. Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress2, 3 and metabolic disorders4-6. How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat diet (HFD)-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m5C, m2G) in sperm 30-40nt RNA fractions that are induced by HFD. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNA-28S), which might be essential in composing a sperm RNA ‘coding signature’ that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m5C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.
2018-03-06 | GSE97645 | GEO
Project description:Intergenerational genomic DNA methylation patterns in mouse hybrid strains Reduced representation bisulfite sequencing from mouse liver, using MspI restriction enzyme, and selecting ~100-300bp size fraction.
2013-12-30 | E-GEOD-53714 | biostudies-arrayexpress
Project description:In animals, maternal diet and environment can influence the health of offspring. Whether and how maternal dietary choice impacts the nervous system across multiple generations is not well understood. Here, we show that feeding Caenorhabditis elegans with ursolic acid (UA), a natural plant product, reduces adult-onset neurodegeneration intergenerationally. UA provides neuroprotection by enhancing maternal provisioning of sphingosine-1-phosphate (S1P) - a bioactive sphingolipid. Intestine-to-oocyte S1P transfer is required for intergenerational neuroprotection and is dependent on the RME-2 lipoprotein yolk receptor. S1P acts intergenerationally by upregulating transcription of the acid ceramidase-1 (asah-1) gene in the intestine. Spatially regulating sphingolipid metabolism is critical as inappropriate asah-1 expression in neurons causes developmental axon outgrowth defects. Our results show that sphingolipid homeostasis impacts the development and intergenerational health of the nervous system. The ability of specific lipid metabolites to act as messengers between generations may have broad implications for dietary choice during reproduction.
2023-06-26 | GSE214425 | GEO
Project description:Piwi Argonautes and Piwi-interacting RNAs (piRNAs) mediate genome defense by targeting transposons. However, many piRNA species lack obvious sequence complementarity to transposons or other loci. For example, only one C. elegans transposon is a known piRNA target. Here we show that, in mutants lacking the Piwi Argonaute PRG-1 and associated piRNAs (21U-RNAs), many silent loci in the germline exhibit increased levels of mRNA expression and depletion of an amplified RNAdependent RNA polymerase (RdRP)-derived species of small RNA termed 22G-RNAs. Sequences depleted of 22G-RNAs are enriched nearby potential target sites that base pair imperfectly but extensively to 21U-RNAs. We show that PRG-1 is required to initiate, but not to maintain, silencing of transgenes engineered to contain complementarity to endogenous 21U-RNAs. Our findings support a model in which C. elegans piRNAs utilize their enormous repertoire of targeting capacity to scan the germline transcriptome for foreign sequences, while endogenous germline-expressed genes are actively protected from piRNA-induced silencing. Examine small RNA population changes in prg-1 and rescued strains
2012-09-01 | E-GEOD-38723 | biostudies-arrayexpress
Project description:Piwi Argonautes and Piwi-interacting RNAs (piRNAs) mediate genome defense by targeting transposons. However, many piRNA species lack obvious sequence complementarity to transposons or other loci. For example, only one C. elegans transposon is a known piRNA target. Here we show that, in mutants lacking the Piwi Argonaute PRG-1 and associated piRNAs (21U-RNAs), many silent loci in the germline exhibit increased levels of mRNA expression and depletion of an amplified RNAdependent RNA polymerase (RdRP)-derived species of small RNA termed 22G-RNAs. Sequences depleted of 22G-RNAs are enriched nearby potential target sites that base pair imperfectly but extensively to 21U-RNAs. We show that PRG-1 is required to initiate, but not to maintain, silencing of transgenes engineered to contain complementarity to endogenous 21U-RNAs. Our findings support a model in which C. elegans piRNAs utilize their enormous repertoire of targeting capacity to scan the germline transcriptome for foreign sequences, while endogenous germline-expressed genes are actively protected from piRNA-induced silencing.
2012-09-01 | GSE38723 | GEO