Alternative somatic and germline gene-regulatory strategies during starvation-induced developmental arrest
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ABSTRACT:
PROVIDER: PRJNA726545 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14370300_1.fastq.gz | Fastqsanger.gz | |||
| SRR14370300_2.fastq.gz | Fastqsanger.gz | |||
| SRR14370301_1.fastq.gz | Fastqsanger.gz | |||
| SRR14370301_2.fastq.gz | Fastqsanger.gz | |||
| SRR14370302_1.fastq.gz | Fastqsanger.gz |
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Project description:Nutrient availability governs growth and quiescence, and many animals arrest development when starved. Using C. elegans L1 arrest as a model, we show that gene expression changes deep into starvation. Surprisingly, relative expression of germline-enriched genes increases for days. We conditionally degrade the large subunit of RNA polymerase II using the auxin-inducible degron system and analyze absolute expression levels. We find that somatic transcription is required for survival, but the germline maintains transcriptional quiescence. Thousands of genes are continuously transcribed in the soma, though their absolute abundance declines, such that relative expression of germline transcripts increases given extreme transcript stability. Aberrantly activating transcription in starved germ cells compromises reproduction, demonstrating important physiological function of transcriptional quiescence. This work reveals alternative somatic and germline gene-regulatory strategies during starvation, with the soma maintaining a robust transcriptional response to support survival and the germline maintaining transcriptional quiescence to support future reproductive success.
| S-EPMC9608353 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-10-11 | GSE173657 | GEO
Project description:Comparison of collection strategies for germline analysis
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Project description:It is widely believed that, owing to the limitation of nutrients in natural environments, bacteria spend most of their life in a non-growing state. However, despite its major clinical and ecological implications, very little is known about what determines the phenotype of starved bacteria, in particular what controls the concentration of different gene products inside the cells. Using microfluidics and quantitative fluorescence microscopy, we monitored growth and gene expression in many independent E. coli lineages as we switched them from exponential growth to starvation. We observed that all cells stopped growing immediately and that no cell death occurred for more than two days. At the same time, gene expression undergoes a dramatic remodeling upon entry into starvation in a promoter-dependent manner. Some promoters, including ribosomal protein promoters, arrest gene expression immediately, others show a slow exponential decay of expression on a 10 h time scale, while a third category exhibits a transient burst of activity before decaying exponentially. Remarkably, the time dynamics of these changes are highly homogeneous across single cells.
In addition, we demonstrated that the gene expression response does not qualitatively depend on the dynamics of starvation entry.
Combining the observed time-dependent protein production and decay rates, we showed with mathematical modeling that a delay between growth arrest and shutdown of gene expression allows a massive increase in the concentration of certain proteins without requiring an upregulation of their expression. Moreover, protein concentrations deep in starvation appeared to be mainly determined by the expression dynamics during the first 10 h of starvation. Finally, we established that this expression program at the onset of starvation is critical for cell viability. In particular, by inhibiting gene expression during different periods of starvation, we were able to show that the tolerance to stress after 2 days is determined by gene expression occurring during the first 10 h, which thus constitutes a preventive response.
These results provide a starting point for quantitative studies of cell maintenance and the emergence of specific phenotypes when nutrients become scarce.
2024-08-23 | MSV000095680 | MassIVE
Project description:Post-embryonic development of the nematode C. elegans is governed by nutrient availability. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This “L1 arrest” (or "L1 diapause") is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. daf-16/FOXO had overlapping but distinct effects on gene expression in L1 arrest compared to daf-2/InsR adults. Notably, dbl-1/TGF-β, a ligand for the Sma/Mab pathway, and daf-36, which encodes an upstream component of the daf-12/NHR steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β and daf-36. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype, and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall, this study shows that daf-16/FOXO promotes developmental arrest cell-nonautonomously by repressing pathways that promote larval development.
2016-05-27 | GSE69329 | GEO
Project description:Germline development provides the founding cells for spermatogenesis and oogenesis in males and females, respectively. Disrupted germline differentiation or compromised testis development can lead to subfertility or infertility and are strongly associated with testis cancer in humans. In mice, SRY and SOX9 induce expression of a range of genes, including Fgf9, that promote Sertoli cell differentiation and testis development. FGF9 is also thought to promote male germline differentiation but the pathway through which it signals is unknown. As FGFs signal through Mitogen-Activated Protein Kinases (MAPKs) in other tissues, we explored whether FGF9 regulates male germline development through MAPK by inhibiting either FGF or MEK1/2 signalling in fetal testis cultures from embryonic day (E)12.5, immediately after gonadal sex determination and testis cord formation, but prior to male germline commitment. Inhibition of MEK1/2 disrupted mitotic arrest, dysregulated a broad range of male germline development genes and prevented the upregulation of key male germline markers DPPA4 and DNMT3L. In contrast, when FGF signalling was inhibited, the male germline specific transcriptional program and the expression of male germline markers DPPA4 and DNMT3L were unaffected, and the germ cells entered mitotic arrest normally. While male germline development was not disrupted by FGF inhibition, a significant number of genes were commonly altered after 24h of FGF or MEK1/2 inhibition including genes involved in maintenance germline stem cells, Nodal signalling, proliferation, and germline cancer. Together, these data demonstrate a novel and essential role for MEK1/2 signalling in male germline differentiation, but a surprisingly limited role for FGF signalling. Our data strongly indicate that additional ligands act through MEK1/2 to promote male germline differentiation and highlight a need for further mechanistic understanding of male germline development.
2023-11-21 | GSE221458 | GEO
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.
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Project description:Nutrient-starvation induced lipid accumulation has been reported in diverse algae, including diatoms. Molecular mechanisms underlying lipid accumulation in nutrient-starved algae are of interest to inform genetic engineering strategies aimed at improving lipid productivity. Diatom cell walls are made of nanostructured silica which is a unique feature of the group and silicon deprivation induces both growth arrest and lipid accumulation. In this work, we report the whole cell transcript level response during silicon starvation induced lipid accumulation.
2015-12-31 | GSE75651 | GEO
Project description:Nutrient-starvation induced lipid accumulation has been reported in diverse algae, including diatoms. Molecular mechanisms underlying lipid accumulation in nutrient-starved algae are of interest to inform genetic engineering strategies aimed at improving lipid productivity. Diatom cell walls are made of nanostructured silica which is a unique feature of the group and silicon deprivation induces both growth arrest and lipid accumulation. In this work, we report the whole cell transcript level response during silicon starvation induced lipid accumulation. Analyzed mRNA from cells after 0, 4, 8, 12, 18, and 24 hr of silicon starvation using the Affymetrix GeneChip whole genome tiling array. Initial analysis of gene level expression was performed using the Affymetrix Expression Console Software, version 1.1. No biological replicates were performed. 0 hr is used as a reference point.
2015-12-31 | E-GEOD-75651 | biostudies-arrayexpress
Project description:Starvation is a severe form of malnutrition that occurs when an individual's intake of food is inadequate to meet their body's energy requirements. Prolonged starvation can cause permanent organ damage, stunted growth in children, and death if left untreated. It is estimated that approximately 45% of deaths among children under the age of 5 years are linked to undernutrition. Notably, the liver’s health is compromised during starvation. More than 60 years ago, it was recognized that chronic severe malnutrition in children, such as kwashiorkor, leads to fatty liver. Subsequently, starvation has been shown to induce accumulation of liver fat (steatosis) in drosophila, zebrafish, and humans. To uncover potential strategies for protecting the liver, we turned to adaptation strategies present in a genetically tractable and naturally occurring model of starvation resistance - the Astyanax mexicanus model system. Cave populations of this species have adapted to survive in conditions of extreme starvation, while the surface populations of the same species display relatively normal vertebrate physiology. We took advantage of this unique system to study the response of the liver to starvation and identified reduced expression of the fatty acid uptake gene slc27a2a/fatp2 allowing cavefish to prevent liver damage under starvation. Targeting this pathway in both fish and flies mitigates starvation-induced hepatic steatosis and protects the liver from lipotoxicity in zebrafish. This demonstrates that the identified pathway is evolutionary conserved for over 400 million years, highlighting its potential as a druggable target.
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