Profiling the piRNA transcriptome of the human brain
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB71709 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR12409217.fastq.gz | Fastqsanger.gz | |||
| ERR12409218.fastq.gz | Fastqsanger.gz | |||
| ERR12409219.fastq.gz | Fastqsanger.gz | |||
| ERR12409220.fastq.gz | Fastqsanger.gz | |||
| ERR12409221.fastq.gz | Fastqsanger.gz |
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Project description:Piwi‑interacting RNAs (piRNAs) comprise the largest class of non‑coding RNAs. They represent a molecular feature shared by all non‑aging biological systems, including germline and somatic cancer stem cells, which display an indefinite capacity of renewal and proliferation and are potentially immortal. They have been identified in animal stomachs, but their relationship with human gastric cancers remains largely unclear. The present study aimed to identify the piRNAs associated with human gastric cancers across the whole transcriptome. Fresh tumor tissues and adjacent non‑tumorous tissues from stomachs were examined using a piRNA microarray (23,677 piRNAs) that was then validated by qPCR. The differential expression of piRNAs between cases and controls was analyzed. The transposable elements (TEs) that are potentially targeted by the risk piRNAs were searched. The expression of the nearest genes that are complementary to the sequences of the piRNAs was examined in the stomach tissue. The regulatory effects of genome‑wide significant and replicated cancer‑risk DNA variants on the piRNA expression in stomach were tested. Based on the findings, we identified a total of 8,759 piRNAs in human stomachs. Of all, 50 were significantly (P<0.05) and differentially (>2‑fold change) expressed between the cases and controls, and 64.7% of the protein‑coding genes potentially regulated by the gastric cancer‑associated piRNAs were expressed in the human stomach. The expression of many cancer‑associated piRNAs was correlated with the genome‑wide and replicated cancer‑risk SNPs. In conclusion, we conclude that piRNAs are abundant in human stomachs and may play important roles in the etiological processes of gastric cancers.
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Project description:<p>Comprehensive knowledge about the spatiotemporal dynamics of the brain transcriptome is essential for a better understanding of neurodevelopment, sexual dimorphism, and evolution, as well as our increased susceptibility to certain brain disorders. We generated and analyzed genome-wide exon-level transcriptome data from 16 brain regions of 57 postmortem human brains, spanning from embryonic development to late adulthood and representing males and females of multiple ethnicities. We also performed genome-wide genotyping of 2.5 million SNPs and assessed genome normality for all donors. This study provides a comprehensive, publicly available dataset on the spatiotemporal human brain transcriptome and new insights into the transcriptional foundations of human neurodevelopment.</p>
| phs000406.v1.p1 | EGA
Project description:The ability to distinguish non-self from self is the key characteristic for any defense system. piRNAs function as guardians of the genome by silencing non-self nucleic acids and transposable elements in animals. Many piRNA factors are enriched in perinuclear germ granules, but whether their localization is required for piRNA biogenesis or function is not known. Here we show that GLH/VASA helicase mutants exhibit defects in forming perinuclear condensates containing PIWI and other small RNA cofactors. These mutant animals produce largely normal levels of piRNA but are defective in triggering piRNA silencing. Strikingly, while many piRNA targets are activated in GLH mutants, we observed that hundreds of endogenous genes are aberrantly silenced by piRNAs. This defect in self versus non-self recognition was also observed in other mutants where perinuclear P granules are disrupted. Together, our results argue that perinuclear germ granules function critically to promote the fidelity of piRNA-based transcriptome surveillance in C. elegans and preserve self versus non-self distinction.
2022-08-05 | PXD033506 | Pride
Project description:Single cell transcriptome profiling of the human alcohol-dependent brain samples.
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Project description:Spatiotemporal transcriptome of the human brain
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Project description:During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the post-transcriptional control of gene expression and protein abundance during human corticogenesis remains poorly understood. We addressed this issue by using a dual reporter cell line to isolate neural progenitors and neurons from the telencephalic brain organoid tissue and performed cell type and developmental stage-specific transcriptome and proteome analysis. Integrating the two datasets revealed temporal modules of gene expression during human corticogenesis, both at RNA and protein level. Our multiomics approach reveals novel posttranscriptional regulatory mechanisms crucial for fidelity of cortical development.
2022-10-25 | PXD037106 | Pride
Project description:Discovered in the brains of multiple animal species, piRNAs may contribute to the pathogenesis of neuropsychiatric illnesses. The present study aimed to identify brain piRNAs across transcriptome that are associated with Alzheimer's disease (AD). Prefrontal cortical tissues of 6 AD cases and 6 controls were examined for piRNA expression levels using an Arraystar HG19 piRNA array (containing 23,677 piRNAs) and genotyped for 17 genome-wide significant and replicated risk SNPs. We examined whether piRNAs are expressed differently between AD cases and controls and explored the potential regulatory effects of risk SNPs on piRNA expression levels. We identified a total of 9453 piRNAs in human brains, with 103 nominally (p < 0.05) differentially (>1.5 fold) expressed in AD cases versus controls and most of the 103 piRNAs nominally correlated with genome-wide significant risk SNPs. We conclude that piRNAs are abundant in human brains and may represent risk biomarkers of AD.
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Project description:Transcriptome profiling of the aging fly brain
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Project description:23-29 nt Piwi-interacting RNAs (piRNAs) are crucial components of the ribonucleoprotein complexes which silence the most abundant class of mobile genetic elements in human genome, retrotransposons, in germline (germ) cells. In these cells, antisense piRNAs serve as RNA guides for Piwi proteins, base pairing with transposon RNAs which are subsequently cleaved by Piwi proteins. Germ cells belong to special class of stem cells which ultimately give rise to eggs and sperm and therefore, to next generations. Therefore, piRNAs protect next-generation genomes from devastating mutations caused by transposon insertions. Although, role of piRNAs in germ cells has been studied, functions of piRNAs and their associated proteins in somatic cells are not well understood. Importantly, Piwi proteins are expressed in the fruit fly Drosophila brain and are required for the silencing of transposable elements there, clearly indicating that Piwi-associated piRNAs are involved in this process in the brain. Furthermore, piRNAs have been implicated in the memory formation mechanisms in Aplysia brain. In addition to Piwi proteins, their associated partner, molecular scaffold Tudor protein, participates in piRNA biogenesis in germ cells and it is absolutely required for germline development. However, although tudor gene is expressed in the fly brain, its role in the central nervous system is not understood. In this study, we look at the role of Tudor as an essential player in piRNA biogenesis in Drosophila brain.
2020-11-27 | GSE149748 | GEO
Project description:ObjectivePiwi-interacting RNAs (piRNAs) represent a molecular feature shared by all nonaging biological systems, including the germline and somatic cancer stem cells, which display an indefinite renewal capacity and lifespan-stable genomic integrity and are potentially immortal. Here, we tested the hypothesis that piRNA is a critical genetic determinant of aging in humans.MethodsExpression of transcriptome-wide piRNAs (n=24k) was profiled in the human prefrontal cortex of 12 subjects (84.9±9.5, range 68-100, years of age) using microarray technology. We examined the correlation between these piRNAs' expression levels and age, adjusting for covariates including disease status.ResultsA total of 9,453 piRNAs were detected in brain. Including seven intergenic and three intronic piRNAs, ten piRNAs were significantly associated with age after correction for multiple testing (|r|=0.9; 1.9×10-5≤p≤9.9×10-5).ConclusionWe conclude that piRNAs might play a potential role in determining the years of survival of humans. The underlying mechanisms might involve the suppression of transposable elements (TEs) and expression regulation of aging-associated genes.
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