Epigenetics and individuality: from concepts to causality across timescales

Nature Reviews Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

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C. elegans transgenerational avoidance of P. fluorescens is mediated by the Pfs1 sRNA and vab-1

Science Advances, Journal Year: 2025, Volume and Issue: 11(17)

Published: April 23, 2025

In its natural habitat, Caenorhabditis elegans must distinguish friend from foe. Pseudomonas are abundant in the worm’s environment and can be nutritious or pathogenic. Previously, we found that worms learn to avoid aeruginosa vranovensis through a small RNA (sRNA)–mediated pathway targeting C. gene maco-1 , this behavior is inherited for four generations. Here, show learns transgenerationally another pathogenic bacteria fluorescens 15 (PF15). The PF15 sRNA, Pfs1, targets VAB-1 ephrin receptor 16 nt of perfect match, suggesting evolution distinct bacterial sRNA/ target pair. Knockdown both vab-1 induce avoidance, loss reduces expression, placing genes sRNA-targeted avoidance pathway. Thus, multiple act as sRNAs, expanding possibilities trans-kingdom regulation behavior.

Language: Английский

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Pseudomonas aeruginosa modulates both Caenorhabditis elegans attraction and pathogenesis by regulating nitrogen assimilation

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 10, 2024

Language: Английский

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Perception of a pathogenic signature initiates intergenerational protection

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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Irreproducibility of transgenerational learned pathogen-aversion response inC. elegans

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Abstract Here we report our attempt to replicate reports of transgenerational epigenetic inheritance in Caenorhabditis elegans . Published results from multiple laboratories show that C. adults and their F1 embryos exposed the pathogen Pseudomonas aeruginosa aversion behavior a exposure-dependent increase daf-7/TGFβ reporter gene expression. However, one group persistence elevated daf-7 expression F2, F3, F4 generations. In contrast, failed consistently detect either avoidance response or beyond generation. We did confirm dsRNA transport proteins SID-1 SID-2 are required for intergenerational (F1) avoidance, but not Furthermore, reanalysis RNA seq data provides additional evidence this inherited PA14 may be mediated by small RNAs. The experimental methods well-described, source materials readily available, including samples reporting laboratory, explored variety environmental conditions likely account lab-to-lab variability. None these adjustments altered results. conclude example lacks robustness, response, daf-7p::gfp progeny, requires sid-1 sid-2 , identify candidate siRNAs target genes mediate response.

Language: Английский

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New insights into how parental worms protect their offspring

Cell Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Language: Английский

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Molecular Requirements for C. elegans Transgenerational Epigenetic Inheritance of Pathogen Avoidance

eLife, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

C. elegans’ major food source is bacteria, and worms are naturally attracted to many bacterial species, including pathogenic Pseudomonas ; in fact, prefer PA14 as well wild bacteria over the lab E. coli strain (OP50) standardly used laboratory setting. Many labs have shown that despite this natural attraction PA14, prior exposure causes instead avoid PA14. This behavioral switch can happen on a relatively fast time scale, even within duration of choice assay. Here we show accurate assessment animals’ true first requires use paralytic (azide) trap at their initial choice, prevent from avoidance assay period. We previously discovered elegans 25°C plate-grown 20°C for 24hrs not only leads these animals switching but also progeny avoiding naïve state, persists through F4 generation. Other types training cause P0 and/or F1 avoidance, do induce transgenerational (F2 beyond) inheritance. showed (P0-F4) learned mediated by P11, small RNA produced P11 both necessary sufficient epigenetic inheritance behavior. highly expressed our standard growth conditions (25°C surfaces), other conditions, suggesting reported failure observe F2-F4 most likely due absence expression experimenters’ conditions. Through mutant analyses, tested genes – germline regulators, uptake, interference/processing, chromatin modifiers, neuronal - involvement pathogen allowing us better understand molecular requirements process. found strains TEI least two P. vranovensis fluorescens 15, avoidance. The induced each species functions specific, distinct (Pv1 Pfs1 15 , respectively) either directly or indirectly reduce levels gene maco-1 which turn regulates daf-7 ASI neuron subsequent conservation multiple components mechanism across suggests behavior be functional physiologically important

Language: Английский

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A novel role of Arp2/3 complex in the forgetting behavior of Caenorhabditis elegans to Pseudomonas aeruginosa PA14

Journal of Neurogenetics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: May 1, 2025

Forgetting behavior is a common phenomenon that has been widely studied in various model organisms, including Caenorhabditis elegans (C. elegans), Drosophila, and mammals such as mice humans. Understanding the mechanisms underlying forgetting can provide valuable insights into potential treatments for memory-related disorders. In this study, C. was used organism to establish based on PA14 pathogen. A proteomic analysis of signaling pathways involved revealed role Arp2/3 complex regulating pathogen-induced forgetting. Manipulation genes encoding components (arx-1, arx-2, arx-3, arx-5, arx-7) led reduction duration Additionally, one hour after pathogen removal, significant decrease mRNA levels arx-5 arx-7 observed, along with arx-2::mCherry fluorescence specific tissues elegans. This study demonstrates exhibits towards PA14, approximately 2 hours. Pathogen-induced associated an increase heterogeneous proteins localized cytoskeleton. Moreover, expression related are reduced, inhibiting cytoskeleton nucleation cells. inhibition may contribute observed response PA14.

Language: Английский

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Absence of Evidence is Not Evidence of Absence: The many flaws in the case against transgenerational epigenetic inheritance of pathogen avoidance inC. elegans

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 7, 2024

Abstract After examining the data and methods presented in Gainey, et al., bioRxiv , 2024 1 we conclude that authors did not use an experimental paradigm would have allowed them to replicate our results on transgenerational epigenetic inheritance (TEI) of learned avoidance regularly observe 2–5 . That is, agree with their experiments show no evidence TEI. However, there are substantial differences execution every step work also make it impossible for claim they replicating or protocols. Based these differences, do believe is issue “robustness” “reliability” TEI findings, but rather Hunter colleagues fact tested central condition - small RNA production by bacteria subsequent uptake C. elegans nor carried out proper behavioral imaging assays assess this behavior. Our shows indeed example just observed laboratory settings PA14, induced wild strains Pseudomonas exhibiting its robustness. Just as offered advice training colleagues, happy advise anyone who wishes learn assay. We now performed absence azide, a deviation from protocol deliberately made, found omission may account most if all results. It disingenuous used protocol, given chose same conditions basic assay work, chemotaxis assay, which been necessary order reproduce work. Therefore, Gainey al.’s claims “irreproducible” supported evidence.

Language: Английский

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Reported transgenerational responses to Pseudomonas aeruginosa in C. elegans are not robust

Published: Dec. 9, 2024

Here we report our attempt to replicate reports of transgenerational epigenetic inheritance in Caenorhabditis elegans . Published results from multiple laboratories show that C. adults and their F1 embryos exposed the pathogen Pseudomonas aeruginosa aversion behavior a exposure-dependent increase daf-7/TGFβ reporter gene expression. However, one group persistence elevated daf-7 expression F2, F3, F4 generations. In contrast, failed consistently detect either avoidance response or beyond generation. We did confirm dsRNA transport proteins SID-1 SID-2 are required for intergenerational (F1) avoidance, but not Furthermore, reanalysis RNA seq data provides additional evidence this inherited PA14 may be mediated by small RNAs. The experimental methods well-described, source materials readily available, including samples reporting laboratory, explored variety environmental conditions likely account lab-to-lab variability. None these adjustments altered results. conclude example lacks robustness, response, daf-7p::gfp progeny, requires sid-1 sid-2 , identify candidate siRNAs target genes mediate response.

Language: Английский

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