PLOS Biology: New Articles
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A single-cell transcriptomic atlas reveals the emergence of medusa-specific cell states in the <i>Aurelia coerulea</i> scyphozoan
by Oliver Link, Stefan M. Jahnel, Kristin Janicek, Daniel Guerguerian, Johanna Kraus, Juan D. Montenegro, Bob Zimmermann, Brittney Wick, Konstantin Khalturin, Alison G. Cole, Ulrich Technau
The life cycle of most medusozoan cnidarians is marked by the metagenesis from the asexually reproducing sessile polyp and the sexually reproducing motile medusa. At present, it is unknown to what extent this drastic morphological transformation is accompanied by molecular changes in the cell type composition. Here, we provide a single-cell transcriptome atlas of the cosmopolitan scyphozoan Aurelia coerulea focusing on changes in individual cell states during the transition from polyp to medusa. Notably, this transition is marked by an increase in cell type diversity, including an expansion of neural subtypes and the appearance of striated muscles. We find that two families of neuronal lineages are specified by homologous transcription factors in the sea anemone Nematostella vectensis and A. coerulea, suggesting an origin in the common ancestor of medusozoans and anthozoans about 500 Myr ago. Our analysis suggests that gene duplications might be drivers for the increase of cellular complexity during the evolution of cnidarian neuroglandular lineages and highlights the close relationship of neurons and muscles. One key medusozoan-specific cell type is the striated muscle in the subumbrella. Evaluating muscle types by fiber anatomy and gene expression validation of their individual molecular profiles made it possible for the first time to investigate transcriptome differences between smooth and striated muscles. Although smooth and striated muscles are phenotypically different, both have a similar regulation of the contractile complex, reminiscent to the regulation of smooth muscles in bilaterians. This contrasts with bilaterian striated muscles, where the regulation of muscle contraction involves Ca2+ binding troponins and their interaction with Tropomyosin. These data suggest that smooth muscle contraction regulation is ancestral and the use of troponins in striated muscles only evolved in bilaterians. -
Stress granules formed during infections with RNA viruses have significant virus-specific differences in generation and composition
by Reto M. Lang, Silvio Steiner, Jenna Kelly, Anne-Christine Uldry, Pratik Dave, Sophie Braga-Lagache, Jeffrey Chao, Manfred Heller, G. Tuba Barut, Volker Thiel
Eukaryotic cells evolved a cellular stress response to cope with extrinsic and intrinsic stress stimuli including virus infections. The major result of this response is the shutdown of bulk translation to prevent damage and allow the reprogramming of translation towards stress-resolving pathways. The resulting translationally stalled mRNA and associated proteins are accumulated in membrane-less cytosolic condensates called stress granules (SG). While the inhibitory effect of translation arrest on virus growth is well established, the role of SGs in the cellular defense against viruses is still unclear. The observation of specific interference with SG formation during various virus infections led to the hypothesis that SGs could serve as antiviral signaling platforms. In this study, we used mouse hepatitis virus (MHV) to characterize SGs formed during coronavirus infection. By applying APEX2-mediated proximity labeling in combination with quantitative proteomics, we dissected the proteome of MHV-induced granules and compared it to canonical SGs formed during oxidative stress. Our data revealed substantial differences in protein abundance and composition, indicating stressor-specific SG characteristics. To assess if the observed differences are a general feature of virus-induced SGs or rather virus-specific, we extended our investigations to the Semliki Forest virus (SFV), a member of the alphavirus family known to induce SGs. An initial comparison of SG formation kinetics by live-cell imaging showed distinct time points of SG induction between both viruses. A comprehensive comparison of the SG protein compositions revealed profound differences in the SG proteome between SFV and MHV. A further subcellular localization of SG components by microscopy not only confirmed a reduced abundance of several translation initiation factors in MHV-induced granules, but surprisingly, revealed the presence of SFV RNA and the absence of MHV RNA in virus-induced SGs. The reduced connection to canonical SG themes observed for MHV-induced granules compared to SFV- and oxidative stress-induced ones indicates a different impact of these condensates on MHV replication and further raises the question whether they should be considered SGs. The surprising plasticity of SGs concerning induction kinetics, protein composition and abundance, and inclusion or exclusion of viral RNA provide a base for future investigations of the role(s) of SGs in the context of viral infection and how they may impact virus replication. -
The gut takes it all: Enteroendocrine control of developmental growth
by Julia B. Cordero
How developing animals sense nutritional shortages to adjust growth? A new study in PLOS Biology shows that the developing intestine is a central regulator of animal growth in response to microbiome composition and nutritional deficiency. How do developing animals sense nutritional shortages and adjust their growth accordingly? A new study in PLOS Biology shows that the developing intestine is a central regulator of a multi-organ signalling coordinating animal growth in response to microbiome composition and nutritional deficiency. -
A nutrient-sensitive enterokine coordinates developmental plasticity through inter-organ signaling
by Longwei Bai, Jacques Montagne, Cathy Isaura Ramos, François Leulier
Animal survival in fluctuating environments depends on the ability to modulate their developmental pace in response to nutrient availability, a phenomenon known as developmental plasticity. In Drosophila larvae, we uncover a critical endocrine mechanism that coordinates this process under conditions of amino acid restriction. We identify the peptide hormone Limostatin as an enterokine, produced by a small population of larval midgut enteroendocrine cells, that acts systemically to inhibit the expression and release of dIlp2, a major insulin-like peptide controlling developmental progression. Limostatin expression and secretion by enteroendocrine cells is triggered by reduced amino acid availability through an inter-organ relay involving the fat body and neuroendocrine insulin-producing cells in the brain. In turn, Limostatin participates in a feedback control loop that slows down developmental progression once systemic nutrient shortage is sensed. This bidirectional gut–brain axis enables larvae to preserve viability under nutritional stress. Our findings define the larval gut as a nutrient-sensitive endocrine organ and position Limostatin as a key regulator of developmental plasticity. Our work expands the concept of decretins to include developmental pace control, suggesting that enterokines that regulate IGF signaling, rather than insulin release per se, may represent an evolutionarily conserved or convergent strategy in regulating developmental plasticity. -
Towards a research renaissance: Empowering early career researchers through mentored AI use
by Douglas R. Call, Mary Sanchez-Lanier, Ananth Kalyanaraman, Sascha H. Duttke
Generative artificial intelligence (AI) is transforming the traditional apprenticeship-style approach to training researchers by lowering technical barriers. When paired with careful mentoring, AI can help early-career researchers engage more quickly in scientific inquiry. Generative AI is transforming the traditional apprenticeship-style approach to training researchers by lowering technical barriers. This Perspective argues that, when paired with careful mentoring, AI can help early career researchers engage more quickly in scientific inquiry.