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Antonova, O.

Publications and source records attributed to Antonova, O..

5 recordsLinked to original sources

Stage-specific transcriptomics of a leader cell reveals cell machineries driving collective invasion

Collective cell invasion underlies organ development, epithelial repair, and cancer metastasis. "Leader cells" remodel extracellular matrix, sense guidance cues, reorganize their cytoskeleton, and coordinate follower cells, but the molecular programs enabling these functions remain unclear. Here, we present a stage-specific transcriptomic dataset of the C. elegans gonadal leader cell, the distal tip cell (DTC), which invades basement membrane and guides germ cells to form U-shaped gonadal arms. Comparing invasive larval-stage DTCs with non-invasive adult-stage DTCs defines the molecular signature of an actively invading leader cell in vivo. Our dataset recapitulates known regulators of gonad morphogenesis and reveals numerous uncharacterized genes with potential roles in leader cell activity. As proof of concept, we identify vesicular trafficking proteins as enriched in invading DTCs, and demonstrate their importance for gonad development using endogenous tagging and DTC-specific RNAi. We also catalog diverse DTC-specific knockdown phenotypes. This resource establishes a molecular framework for leader cell activity and a platform to investigate conserved mechanisms of invasive migration.

developmental biology↗

Neuronal oversight of germline small RNAs prevents heat-induced sterility in lab-domesticated Caenorhabditis elegans

Thermal pollution, whether local or driven by global warming, threatens biodiversity in part through its detrimental effects on reproduction. Non-coding small RNAs (sRNAs) are crucial for maintaining germline developmental robustness under heat stress. Remarkably, we uncovered that neuronal sRNAs regulate germ cells thermotolerance, affecting both spermatogenic and oogenic germline in a cell non-autonomous manner. Furthermore, we demonstrate that an oxygen-sensing neural circuit antagonizes germline maintenance, likely reflecting the nematodes innate association of reduced oxygen levels with food availability and reproductive permissive environments. Finally, we provide evidence that sRNAs buffer the negative consequences of laboratory domestication, which otherwise cause the laboratory strain to lose germline integrity and become sterile at elevated temperatures. Hence, our findings reveal that mere sensory perception, independent of direct environmental change, modulates germline integrity through sRNA pathways, highlighting a novel mechanism by which neural circuits integrate environmental information to safeguard reproductive fitness in fluctuating environments.

genetics↗

Heritable Sexual Attraction under Parental Control

It is unknown whether transient transgenerational epigenetic responses to environmental challenges affect the process of evolution, which typically unfolds over many generations. Here we show that in C. elegans, inherited small RNAs shape the hard-wired genome and control genetic variation by regulating the decision of whether to self-fertilize or outcross. We found that under stressful temperatures younger hermaphrodites secrete a male-attracting pheromone. Attractiveness transmits transgenerationally to unstressed progeny via heritable small RNAs and the Argonaute Heritable-RNAi-Deficient-1. We identified an endogenous small interfering RNA pathway, enriched in endo-siRNAs which target sperm genes, that transgenerationally regulates sexual attraction, male prevalence, and outcrossing rates. Multigenerational mating competitions and mathematical simulations revealed that over generations, animals that inherit attractiveness mate more, and their alleles spread in the population. We propose that sperm serves as a "stress sensor" which, via small RNA inheritance, can promote outcrossing in challenging environments, when increasing genetic variation is advantageous.

molecular biology↗

Three Rules Explain Transgenerational Small RNA Inheritance in C. elegans

Life experiences trigger transgenerational small RNA-based responses in C. elegans nematodes. Dedicated machinery ensures that heritable effects would re-set, typically after a few generations. Here we show that isogenic individuals differ dramatically in the persistence of transgenerational responses. By examining lineages composed of >20,000 worms we reveal 3 inheritance rules: (1) Once a response is initiated, each isogenic mother stochastically assumes an "inheritance state", establishing a commitment that determines the fate of the inheritance. (2) The response that each mother transfers is uniform in each generation of her descendants. (3) The likelihood that an RNAi response would transmit to the progeny increases the more generations the response lasts, according to a "hot hand" principle. Mechanistically, the different parental "inheritance states" correspond to global changes in the expression levels of endogenous small RNAs, immune response genes, and targets of the conserved transcription factor HSF-1. We show that these rules predict the descendants developmental rate and resistance to stress.

genetics↗

Platelet, erythrocyte, endothelial, and monocyte microparticles in coagulation activation and propagation

Background and objectiveFor many pathological states, microparticles are supposed to be one of the causes of hypercoagulation. Although there are some indirect data about microparticles participation in coagulation activation and propagation, the integral hemostasis test Thrombodynamics allows to measure micropaticles participation in these two coagulation phases directly by influence on the appearance of coagulation centers in plasma volume and on the rate of clot grown from surface with immobilized tissue factor. MethodsMicroparticles were obtained from platelets and erythrocytes by stimulation with SFLLRN and A23187, respectively, from monocytes, endothelial HUVEC culture and monocytic THP cell culture by stimulation with lipopolysaccharides. Microparticles were counted by flow cytometry and titrated in microparticle-depleted normal plasma in the Thrombodynamics test. ResultsMonocyte microparticles induced the appearance of clotting centres through the TF pathway at concentrations approximately 100-fold lower than platelet and erythrocyte microparticles, which activated plasma by the contact pathway. For endothelial microparticles, both activation pathways were essential, and their activity was intermediate. Monocyte microparticles induced plasma clotting by the appearance of hundreds of clots with an extremely slow growth rate, while erythrocyte microparticles induced the appearance of a few clots with a growth rate similar to that from surface covered with high-density tissue factor. Patterns of clotting induced by platelet and endothelial microparticles were intermediate. Platelet, erythrocyte and endothelial microparticles impacts on the rate of clot growth from the surface with tissue factor did not differ significantly within the 0-200{middle dot}103/ul range of microparticles concentrations. However, at concentrations greater than 500{middle dot}103/ul, erythrocyte microparticles increased the stationary clot growth rate to significantly higher levels than do platelet microparticles or artificial phospholipid vesicles consisting of phosphatidylcholine and phosphatidylserine. ConclusionMicroparticles of different origins demonstrated qualitatively different characteristics related to coagulation activation and propagation.

biophysics↗