The germline regulates longevity and somatic repair in a sex-specific manner (RNA-Seq)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1045687 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26962000.fastq.gz | Fastqsanger.gz | |||
| SRR26962001.fastq.gz | Fastqsanger.gz | |||
| SRR26962002.fastq.gz | Fastqsanger.gz | |||
| SRR26962003.fastq.gz | Fastqsanger.gz | |||
| SRR26962004.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:The germline regulates longevity and somatic repair in a sex-specific manner
| PRJNA1045681 | ENA
Project description:Classical evolutionary theories propose tradeoffs between reproduction, damage repair, and lifespan. However, the specific role of the germline in shaping vertebrate aging remains largely unknown. Here, we use the turquoise killifish (N. furzeri) to genetically arrest germline differentiation at discrete stages, and examine how different ‘flavors’ of infertility impact life-history. We first constructed a comprehensive single-cell gonadal atlas, providing cell-type-specific markers for downstream phenotypic analysis. Next, investigating our genetic models revealed that only germline ablation enhanced female damage repair, while arresting germline differentiation did not. Conversely, germline-ablated males were significantly long-lived, indicating that the mere presence of the germline can negatively affect lifespan. Transcriptomic analysis highlighted enrichment of pro-longevity pathways and genes, with functional conservation in germline-ablated C. elegans. Finally, germline depletion extended male healthspan through rejuvenated metabolic functions. Our results suggest that different germline manipulation paradigms can yield pronounced sexually dimorphic phenotypes, implying alternative mechanisms to classical evolutionary tradeoffs.
2024-03-06 | GSE248739 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-03-06 | GSE248741 | GEO
Project description:How lifespan and the rate of aging are set is a key problem in biology. Small RNAs are conserved molecules that impact diverse biological processes through the control of gene expression. However, in contrast to miRNAs, the role of endo-siRNAs in aging remains unexplored. Here, by combining deep sequencing and genomic and genetic approaches in C. elegans, we reveal an unprecedented role for endo-siRNA molecules in the maintenance of proteostasis and lifespan extension in germline-less animals. Furthermore, we identify an endo-siRNA-regulated tyrosine phosphatase, which limits the longevity of germline-less animals by restricting the activity of the heat shock transcription factor HSF-1. Altogether, our findings point to endo-siRNAs as a link between germline removal and the HSF-1 proteostasis and longevity-promoting somatic pathway. This establishes a role for endo siRNAs in the aging process and identifies downstream genes and physiological processes that are regulated by the endo siRNAs to affect longevity.
2020-04-03 | GSE122457 | GEO
Project description:How lifespan and the rate of aging are set is a key problem in biology. Small RNAs are conserved molecules that impact diverse biological processes through the control of gene expression. However, in contrast to miRNAs, the role of endo-siRNAs in aging remains unexplored. Here, by combining deep sequencing and genomic and genetic approaches in C.CaenorhabditisC. elegans elegans, we reveal an unprecedented role for endo-siRNA molecules in the maintenance of proteostasis and lifespan extension in germline-less animals. Furthermore, we identify an endo-siRNA-regulated tyrosine phosphatase, which limits the longevity of germline-less animals by restricting the activity of the heat shock transcription factor HSF-1. Altogether, our findings point to endo-siRNAs as a link between germline removal and the HSF-1 proteostasis and longevity-promoting somatic pathway. This establishes a role for endo siRNAs in the aging process and identifies downstream genes and physiological processes that are regulated by the endo siRNAs to affect longevity.
2020-04-03 | GSE128935 | GEO
Project description:The objective of the study is the provide proof of high correlation between somatic and germline mismatch repair instability. This correlation is specifically researched in an area where patients have less access to cancer education and genetic testing for various reasons such as lack of insurance and general accessibility.
The study concentrates on early diagnosis of Lynch syndrome. Lynch syndrome is usually diagnosed from a blood test resulting in a mutation of one of the mismatch repair genes. Those are MLH1, MSH2, MSH 6, PMS2. A mutation in one of these genes creates a mismatch repair instability,hence higher incidence of cancers in specific organ groups. Amongst these organs are the Uterus, Ovaries, Upper genitourinary system, Pancreas and GI system.
The most common endometrial carcinoma which is found in Lynch syndrome is of endometrioid histology. Most patients with known germline mismatch repair instability, have the same somatic mutation. Our study is looking into correlating somatic mutation to germline mutation.
By doing so, patients diagnosed with somatic mismatch repair instability will be also diagnosed with lynch syndrome without germline genetic testing.
Screening programs will be utilized earlier and preventive procedures offered.
Due to less access to educational programs, genetic counseling and testing in underserved areas, patients are sometimes lost to follow up. Our study seeks to prove high correlation between somatic and germline mutations and by doing so, patient will be diagnosed with Lynch syndrome straight after endometrial cancer staging. As a result, increased compliance will be expected and patients will be offered the recommended preventative surgeries and screening protocols.
| 2349042 | ecrin-mdr-crc
Project description:The plasticity of ageing suggests that longevity may be controlled epigenetically by specific alterations in chromatin state. The link between chromatin and ageing has mostly focused on histone deacetylation by the Sir2 family1, 2, but less is known about the role of other histone modifications in longevity. Histone methylation has a crucial role in development and in maintaining stem cell pluripotency in mammals3. Regulators of histone methylation have been associated with ageing in worms4, 5, 6, 7 and flies8, but characterization of their role and mechanism of action has been limited. Here we identify the ASH-2 trithorax complex9, which trimethylates histone H3 at lysine 4 (H3K4), as a regulator of lifespan in Caenorhabditis elegans in a directed RNA interference (RNAi) screen in fertile worms. Deficiencies in members of the ASH-2 complex—ASH-2 itself, WDR-5 and the H3K4 methyltransferase SET-2—extend worm lifespan. Conversely, the H3K4 demethylase RBR-2 is required for normal lifespan, consistent with the idea that an excess of H3K4 trimethylation—a mark associated with active chromatin—is detrimental for longevity. Lifespan extension induced by ASH-2 complex deficiency requires the presence of an intact adult germline and the continuous production of mature eggs. ASH-2 and RBR-2 act in the germline, at least in part, to regulate lifespan and to control a set of genes involved in lifespan determination. These results indicate that the longevity of the soma is regulated by an H3K4 methyltransferase/demethylase complex acting in the C. elegans germline. There are 23 samples in total. ASH-2 knock-down increases lifespan in a germline dependent manner. We examined ASH-2 regulated genes that are dependent on the presence of an intact germline using WT or glp-1(e2141ts) mutant worms which develop only 5-15 meiotic germ cells treated with either empty vector (EV) or ash-2 RNAi. We examined gene expression at the L3 stage (when we observe changes in H3K4me3) and at a mid life stage (day 8). The majority of ASH-2 controlled genes were regulated in a germline dependent manner. Samples were collected in triplicate for each condition (but Day 8 N2 (WT) E.V. #3 was excluded from all analysis due to quality issues).
2011-07-08 | E-GEOD-30505 | biostudies-arrayexpress
Project description:Somatic piRNA pathway prevents transgenerational germline transposition
| PRJNA449636 | ENA
Project description:In many vertebrate species, age at maturity is proportional to organismal lifespan. A number of theories have attempted to provide a conceptual framework for this fascinating apparent co-evolution. The ‘disposable soma’ theory predicts that costly resources that are invested in germline preservation come at the expense of repairing age-related somatic damage. On the other hand, classical experiments in C. elegans have reported that germline ablation promotes longevity via endocrine signals mediated by the somatic gonad. However, how these seemingly opposing mechanisms may affect vertebrate aging is largely unknown. Here, we use the naturally short-lived turquoise killifish (N. furzeri) to demonstrate that germline ablation can enhance damage repair and promote vertebrate longevity. This was achieved by producing a detailed single-cell atlas of the killifish ovary and testis, and generating a panel of genetic perturbations to manipulate the killifish reproductive state. Specifically, we either block costly stages of germline differentiation by mutating gonadotropins and their receptors, or alternatively, ablate the germline altogether by mutating the dnd1 gene (dead end). Interestingly, only germline ablation enhances somatic repair, particularly in females, by improving tail regeneration following genotoxic stress. To investigate the observed sexual dimorphism, we directly compare several somatic cell types from WT and dnd1 fish. We identify a surprising male-specific upregulation of pro-longevity pathways, including protein homeostasis and stress resistance. Accordingly, only germline-depleted males experience a significant extension in maximal lifespan. Together, dissecting distinct paradigms of germline manipulations, reveals a functional link between the reproductive state, damage repair, and longevity. The sex-specific effect further supports the concept that phenotypes are independent of resource allocation, and instead, could be the result of a possible endocrine effect. Our findings may therefore have exciting implications for uncoupling the reproductive state from vertebrate aging.
2024-03-06 | GSE218622 | GEO
Project description:In C. elegans, the H3K4me2 demethylase, SPR-5, and the H3K9 methyltransferase, MET-2, are maternally deposited into the oocyte where they reprogram histone methylation to prevent somatic expression of germline genes. Here, we show that the progeny of spr-5; met-2 mutants display a severe developmental delay that is associated with the ectopic expression of germline genes targeted by the H3K36me2/3 methyltransferase, MES-4. Maternally deposited MES-4 maintains H3K36me2/3 at a subset of germline genes (hereafter referred to as MES-4 germline genes) in a transcription-independent manner, and this is required for germline proliferation in the subsequent generation. By performing ChIP-seq on L1 progeny from spr-5; met-2 mutants, we find that MES-4 germline genes ectopically accumulate H3K36me3 in somatic tissues. Additionally, knocking down MES-4 suppresses the ectopic expression of MES-4 germline genes and rescues the developmental delay. These data suggest a model where SPR-5, MET-2 and MES-4 carefully balance the inheritance of histone methylation from the parental germline to ensure the proper specification of germline versus soma in the progeny. Without SPR-5; MET-2 maternal reprogramming, somatic cells struggle to specify their proper cell fate amongst the background noise of inappropriate germline gene transcription, leading to a severe developmental delay.
2020-05-29 | GSE151340 | GEO