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Kozlovski, I.

Publications and source records attributed to Kozlovski, I..

4 recordsLinked to original sources

Epigenomic and transcriptomic analyses reveal cnidocyte specialization in a sea anemone

Cnidarians, including corals, hydras, jellyfish, and sea anemones, possess specialized stinging cells called cnidocytes that function in prey capture and defense. These cells represent a striking evolutionary innovation and produce distinct types of organelles such as venom injecting nematocysts and mechanically entangling spirocysts. While their biomechanics and transcriptional regulation have been studied extensively, little is known about their epigenetic regulation. Here, we combined epigenetic profiling with RNA sequencing in the sea anemone Nematostella vectensis to explore regulatory programs underlying cnidocyte diversity. We identified cell-type-specific regulatory elements in promoter and enhancer regions and linked them to distinct gene expression programs. This analysis revealed fundamental differences between nematocytes and spirocytes and uncovered a previously unrecognized nematocyte population that expresses the Nep3 toxin but lacks most other toxins. These findings highlight the complexity of cnidocyte regulation and suggest greater cellular diversity within this defining cnidarian cell type than previously appreciated.

evolutionary biology↗

Functional characterization of immune cells in a cnidarian reveals an ancestral antiviral program

Examining early-branching animal phyla can help reconstructing the evolutionary origins of immune cells. Here, we characterized immune-related cell programs in embryos of the sea anemone Nematostella vectensis, a model of Cnidaria, which diverged [~]600 million years ago from other animals. Using a transgenic Nematostella reporter line expressing mCherry under the RLRb antiviral promoter, we identified a morphologically and transcriptomically distinct cell population activated by the viral mimic poly(I:C). These cells upregulate immune effector and regulator genes and show increased phagocytic activity. Bulk RNA sequencing of RLRb expressing cells and single-cell transcriptomics revealed gene regulatory programs expressed in specialized immune cells under basal conditions and upon activation. Comparing the Nematostella immune expression profile with that of stony corals treated with the immunostimulant 2'3'-Cyclic GMP-AMP demonstrated a conserved immune response across Hexacorallia. This study uncovers a novel cnidarian immune cell type involved in antiviral immunity, providing insights into the evolutionary history of innate immunity.

evolutionary biology↗

Induction of apoptosis by double-stranded RNA was present in the last common ancestor of cnidarian and bilaterian animals

Apoptosis, a major form of programmed cell death, is an essential component of host defense against invading intracellular pathogens. Viruses encode inhibitors of apoptosis to evade host responses during infection, and to support their own replication and survival. Therefore, hosts and their viruses are entangled in a constant evolutionary arms race to control apoptosis. Until now, apoptosis in the context of the antiviral immune system has been almost exclusively studied in vertebrates. This limited phyletic sampling makes it impossible to determine whether a similar mechanism existed in the last common ancestor of animals. Here, we established assays to probe apoptosis in the sea anemone Nematostella vectensis, a model species of Cnidaria, a phylum that diverged approximately 600 million years ago from the rest of animals. We show that polyinosinic:polycytidylic acid (poly I:C), a synthetic long double-stranded RNA mimicking viral RNA and a primary ligand for the vertebrate RLR melanoma differentiation-associated protein 5 (MDA5), is sufficient to induce apoptosis in N. vectensis. Furthermore, at the transcriptomic level, apoptosis related genes are significantly enriched upon poly(I:C) exposure in N. vectensis as well as bilaterian invertebrates. Our phylogenetic analysis of caspase family genes in N. vectensis reveals conservation of all four caspase genes involved in apoptosis in mammals and revealed a cnidarian-specific caspase gene which was strongly upregulated. Altogether, our findings suggest that apoptosis in response to a viral challenge is a functionally conserved mechanism that can be traced back to the last common ancestor of Bilateria and Cnidaria.

evolutionary biology↗

A pan-cnidarian microRNA is an ancient biogenesis regulator of stinging cells

An ancient evolutionary innovation of a novel cell-type, the stinging cell (cnidocyte), appeared >600 million years ago in the phylum Cnidaria (sea anemones, corals, hydroids, and jellyfish). A complex bursting nano-injector of venom, the cnidocyst, is embedded in cnidocytes and enables cnidarians paralyzing prey and predators, contributing to this phylums evolutionary success. In this work, we show that post-transcriptional regulation by a pan-cnidarian microRNA, miR-2022, is essential for biogenesis of these cells. By manipulation of miR-2022 levels in a transgenic reporter line of cnidocytes in the sea anemone Nematostella vectensis, followed by transcriptomics, single-cell data analysis, prey paralysis assays, and cell sorting of transgenic cnidocytes, we reveal that miR-2022 enables cnidocyte biogenesis, while exhibiting a conserved expression domain with its targets in cnidocytes of other cnidarian species. Thus, here we reveal one of natures most ancient microRNA-regulated processes by studying the functional basis for its conservation.

evolutionary biology↗