Biology subjects

Coyne, C.

Publications and source records attributed to Coyne, C..

12 recordsLinked to original sources

bioRxiv2026

Selection For Yield Enhanced Rhizobial Mutualism In Pea

Crop improvement can enhance food security, but side effects, such as trade-offs between valuable agronomic traits, are common. Likewise, fertilisation helps ensure high yields, but can devalue mutualisms with soil microbes that would otherwise be essential for nutrient acquisition. If the need for nutritional mutualisms is reduced in crops, mutualisms could be disrupted by selection relaxation or allocation trade-offs. Thus, crops could achieve high yields in spite of, or because of, disruption of nutritional mutualisms. Alternatively, the highest-yielding plants might flourish because they maximise nutrient acquisition from both symbionts and the soil. Here, enhanced mutualism could evolve over the course of agricultural crop improvement. To investigate whether high yields in cultivars and wild accessions are negatively or positively genetically correlated with outcomes in the legume-rhizobia mutualism, we measured whether yield and symbiosis traits trade-off or are positively genetically correlated among cultivars and wild accessions. We also tested whether this relationship differs between accessions released before or after 1950. We measured genetic correlations between yield and mutualism traits in 87 domesticated pea (Pisum sativum) accessions in a common garden agricultural field across three years. Seed yield and N2 fixation (%Ndfa) were positively genetically correlated. While N fixation was more strongly predictive of yield in the pre-1950 accessions than the post-1950 accessions, the underlying positive genetic correlation between the traits did not differ between the groups. The positive genetic correlation between yield and N2 fixation indicates that selection to increase yields has maintained or increased the benefits of the rhizobial mutualism in pea. Our findings predict that breeding to increase yield may continue to produce pea cultivars that get a greater proportion of their N from rhizobia, enhancing symbiotic mutualism and reducing the proportion of N supplied by fertilisation.

plant biology↗

bioRxiv2026

Genomic and Transcriptomic Basis of Salinity Tolerance in Dry Pea

Salinity is a major crop production constraint in dry pea (Pisum sativum L.), making the development of salt-tolerant varieties essential to improve crop productivity and land-use efficiency. The genetic mechanisms of salt tolerance in dry pea is largely unknown, and research on salt-tolerant genes is limited. In this study, we established comprehensive genomic and transcriptomic resources, along with a robust screening protocol, to dissect the genetic basis of salinity tolerance using two germplasm sets: the USDA pea diversity panel, consisting of approximately 200 globally sourced accessions, and a set of 300 modern elite lines from the NDSU Pulse Crops Breeding Program. Genetic variation for the salinity response was assessed based on ten phenotypic traits, with root dry weight, shoot dry weight, and specific root length identified as key indicators based on their heritability. Genome-wide association mapping uncovered significant genomic regions and several candidate genes linked to salt stress, with the strongest association found on chromosome 6. Overlapping QTL signals across traits suggest a shared genetic architecture underlying salinity tolerance. Field-based transcriptomic analysis further identified five putative genes involved in salinity response conserved across multiple crop species. Notably, Psat5g000800, encoding a glycosyl hydrolase gene, was markedly upregulated under salinity stress. These findings highlight the complex, multi-gene regulatory nature of salinity tolerance in dry pea and underscore the importance of functional validation of candidate genes. This study provides key insights and practical tools to support breeding efforts aimed at improving salt tolerance in dry pea.

genetics↗

bioRxiv2026

Type I and Type III Interferons Differentially Shape Antiviral Defense and Epithelial Integrity at the Choroid Plexus

The choroid plexus (ChP) forms the blood-cerebrospinal fluid (CSF) barrier, yet how this CNS interface responds to viral infection remains poorly understood. Here, we identify the ChP epithelium as a major target of echovirus infection and establish complementary human organoid and mouse models to define antiviral responses at this barrier. Single-cell RNA sequencing of cerebral organoids revealed preferential infection of ChP epithelial cells, and ChP organoids supported productive infection accompanied by a robust type III interferon (IFN) response. In mice expressing human FcRn, the echovirus receptor, infection similarly targeted the ChP, enabling genetic dissection of IFN signaling in vivo. Type I IFN signaling restricted viral replication and protected against lethal disease. In contrast, type III IFN signaling was dispensable for viral control but promoted ChP epithelial injury and, following viral clearance, was associated with persistent motor deficits, ependymal loss, and ventriculomegaly. These findings reveal distinct functions for type I and III IFNs at the blood-CSF barrier and identify type III IFN signaling as a driver of tissue injury and lasting neurological sequelae following viral infection.

immunology↗

bioRxiv2025

Humoral correlates of protection in a mouse model of echovirus infection

Echoviruses commonly infect humans and can cause severe outcomes, including meningitis and liver failure, especially in neonates and immunocompromised individuals. Although recent progress has been made in understanding acute pathogenesis and innate immunity to echoviruses, adaptive immune responses remain poorly defined, in part due to the lack of an appropriate small animal model of infection. Here, we developed a translational mouse model of echovirus infection using hFc mice, which express human FcRn, the echovirus receptor, while maintaining functional IgG circulation. Primary echovirus infection caused acute disease and elicited virus-specific nAbs, IgG, and IgM only in hFc mice, which express human FcRn and support IgG transport, but not in parental Tg32 mice that lack IgG transport. These humoral responses correlated with protection against a homologous lethal-dose challenge. The protective role of these antibodies was confirmed by passive transfer of immune serum, which conferred complete, sterilizing protection. Statistical modeling identified E5-specific nAb, total IgG, and IgG1 titers as the strongest predictors of survival following infection, identifying novel correlates of protection. These findings establish hFc mice as a robust translational model for dissecting echovirus adaptive immunity, define the humoral response to infection, and identify correlates of protection to guide future vaccine development and preclinical evaluation.

immunology↗

bioRxiv2024

Interferon Epsilon Protects Epithelial Barriers from Viral Infection through Autocrine Intracellular Signaling

Antiviral defenses at mucosal barriers are essential for preventing viral entry and systemic infection. Interferon epsilon (IFN{varepsilon}) is a unique type I IFN that, unlike other family members, is not induced by infection but is constitutively expressed in epithelial tissues. IFN{varepsilon} was initially characterized in the female reproductive tract (FRT), where it provides broad antiviral protection, but its roles outside the FRT remain poorly defined. Here, we used Ifn{varepsilon}-/- mice and single-cell RNA sequencing to delineate IFN{varepsilon} function across distinct mucosal surfaces. In the FRT, Ifn{varepsilon} expression was restricted to specific epithelial subsets, was independent of estrous stage, and maintained basal ISG expression. IFN{varepsilon} was also retained intracellularly in primary human FRT-derived cells. Extending these analyses to the intestine, we found that IFN{varepsilon} is highly expressed in villous-tip enterocytes of the small intestine in vivo, where it sustains inflammatory enterocyte subsets and maintains type III IFN expression. Loss of Ifn{varepsilon} depleted these subsets and rendered mice more susceptible to enteric viral infection. Together, these findings establish IFN{varepsilon} as a constitutively expressed, spatially restricted IFN that coordinates mucosal antiviral defenses across both reproductive and gastrointestinal epithelial tissues.

immunology↗

bioRxiv2024

Defining Cellular Diversity at the Swine Maternal-Fetal Interface Using Spatial Transcriptomics and Organoids

The placenta is a dynamic, embryo-derived organ essential for fetal growth and development. While all eutherian mammals have placentas composed of fetal-derived trophoblasts that mediate maternal-fetal exchange, their anatomical and histological structures vary across species due to evolutionary divergence. Despite the cellular heterogeneity of porcine trophoblasts in vivo, understanding the mechanisms driving porcine placental development has been limited by the lack of in vitro models replicating this heterogeneity. In this study, we derived swine trophoblast organoids (sTOs) from full-term porcine placentas, retaining key transcriptional signatures of in vivo trophoblasts. To identify conserved cell populations, we integrated Visium spatial transcriptomics from mid-gestation porcine placentas with single-cell transcriptomics from sTOs. Spatial transcriptomics revealed novel markers of the porcine uterus and placenta, enabling precise separation of histological structures at the maternal-fetal interface. The integration of tissue and sTO transcriptomics showed that sTOs spontaneously differentiate into distinct trophoblast populations, with conserved gene expression and cell communication programs. These findings demonstrate that sTOs recapitulate porcine placental trophoblast populations, offering a powerful model for advancing placentation research. Our work also provides a spatially resolved whole-transcriptome dataset of the porcine maternal-fetal interface, opening new avenues for discoveries in placental development, evolution, and health across mammals.

developmental biology↗

bioRxiv2024

Comparative analysis of rhesus macaque and human placental organoids highlights evolutionary differences in placentation

Throughout evolution, the placenta has diversified in structure and cellular composition while maintaining its essential role in supporting fetal development. Trophoblasts, key cells responsible for nutrient exchange and immune modulation, are a conserved feature of all placentas. Although primate placentas share broad morphological similarities, species-specific differences in gene expression remain poorly characterized, largely due to the lack of tractable in vitro models. To address this gap, we developed rhesus macaque placental organoids representing both trophoblast and maternal-derived decidual cell types and compared them with human placental organoids. Using integrated single-cell and single-nucleus RNA sequencing, we identified both shared and species-specific transcriptional programs across corresponding trophoblast lineages. We further reconstructed lineage trajectories leading to multinucleated syncytiotrophoblast and invasive extravillous trophoblast populations, revealing conserved differentiation pathways alongside divergent gene expression signatures. This work establishes new in vitro models of the nonhuman primate placenta and defines the molecular distinctions between human and rhesus trophoblasts, offering insights into the evolutionary adaptations underlying placental development.

developmental biology↗

bioRxiv2023

Immune Correlates of Hyperglycemia and Vaccination in a Non-human Primate Model of Long-COVID

Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are major manifestations of the post-acute sequelae of SARS-CoV-2 (PASC). Our understanding of lasting glucometabolic disruptions after acute COVID-19 remains unclear due to the lack of animal models for metabolic PASC. Here, we report a non-human primate model of metabolic PASC using SARS-CoV-2 infected African green monkeys (AGMs). Using this model, we have identified a dysregulated chemokine signature and hypersensitive T cell population during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. This persistent hyperglycemia correlates with elevated hepatic glycogen, but there was no evidence of long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the AGM metabolic PASC model exhibits important similarities to human metabolic PASC and can be utilized to assess therapeutic candidates to combat this syndrome.

immunology↗

bioRxiv2023

Trophoblast organoids with physiological polarity model placental structure and function

Human trophoblast organoids (TOs) are a three-dimensional ex vivo culture model that can be used to study various aspects of placental development, physiology, and pathology. Previously, we showed that TOs derived from full-term human placental tissue could be used as models of trophoblast innate immune signaling and teratogenic virus infections. Here, we developed a method to culture TOs under conditions that recapitulate the cellular orientation of chorionic villi in vivo, with the multi-nucleated syncytiotrophoblast (STB) localized to the outer surface of organoids and the proliferative cytotrophoblasts (CTBs) located on the inner surface. We show that standard TOs containing the STB layer inside the organoid (STBin) develop into organoids containing the STB on the outer surface (STBout) when cultured in suspension with gentle agitation. STBout organoids secrete higher levels of select STB-associated hormones and cytokines, including human chorionic gonadotropin (hCG) and interferon (IFN)-{lambda}2. Using membrane capacitance measurements, we also show that the outermost surface of STBout organoids contain large syncytia comprised of >50 nuclei compared to STBin organoids that contain small syncytia (<10 nuclei) and mononuclear cells. The growth of TOs under conditions that mimic the cellular orientation of chorionic villi in vivo thus allows for the study of a variety of aspects of placental biology under physiological conditions.

cell biology↗

bioRxiv2021

Respiratory and intestinal epithelial cells exhibit differential susceptibility and innate immune responses to contemporary EV-D68 isolates

Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and acute flaccid myelitis (AFM) and is detected in patient respiratory samples and from stool and wastewater, suggesting both respiratory and enteric routes of transmission. Here, we used a panel of EV-D68 isolates, including a historical isolate and multiple contemporary isolates from AFM outbreak years, to define the dynamics of viral replication and the host response to infection in primary human airway cells and stem cell-derived enteroids. We show that some recent EV-D68 isolates have decreased sensitivity to acid and temperature compared with an earlier isolate and that the respiratory, but not intestinal, epithelium induces a robust type III interferon (IFN) response that restricts infection. Our findings define the differential responses of the respiratory and intestinal epithelium to contemporary EV-D68 isolates and suggest that some isolates have the potential to target both the human airway and gastrointestinal tracts.

microbiology↗

bioRxiv2020

Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice

Neonatal echovirus infections are characterized by severe hepatitis and neurological complications that can be fatal. Here, we show that expression of the human homologue of the neonatal Fc receptor (hFcRn), the primary receptor for echoviruses, and ablation of type I interferon (IFN) signaling are key host determinants involved in echovirus pathogenesis. We show that expression of hFcRn alone is insufficient to confer susceptibility to echovirus infections in mice. However, expression of hFcRn in mice deficient in type I interferon (IFN) signaling, hFcRn-IFNAR-/-, recapitulate the echovirus pathogenesis observed in humans. Luminex-based multianalyte profiling from E11 infected hFcRn-IFNAR-/- mice revealed a robust systemic immune response to infection, including the induction of type I IFNs. Furthermore, similar to the severe hepatitis observed in humans, E11 infection in hFcRn-IFNAR-/- mice caused profound liver damage. Our findings define the host factors involved in echovirus pathogenesis and establish in vivo models that recapitulate echovirus disease.

microbiology↗

bioRxiv2018

The neonatal Fc receptor is a pan-echovirus receptor

Echoviruses are the main causative agents of aseptic meningitis worldwide and are particularly devastating in the neonatal population, where they are associated with severe hepatitis, neurological disease including meningitis and encephalitis, and even death. Here, we identify the neonatal Fc receptor (FcRn) as a pan-echovirus receptor. We show that loss of expression of FcRn or its binding partner beta 2 microglubulin ({beta}2M) renders human brain microvascular cells resistant to infection by a panel of echoviruses at the stage of virus attachment and that a blocking antibody to {beta}2M inhibit echovirus infection in cell lines and in primary human fetal intestinal epithelial cells. We also show that expression of human, but not mouse, FcRn renders non-permissive human and mouse cells sensitive to echovirus infection and that the extracellular domain of human FcRn directly binds echoviral particles and neutralizes infection. Lastly, we show that primary cells isolated from mice that express human FcRn are highly susceptible to echovirus infection. Our findings thus identify FcRn as a pan-echovirus receptor, which may explain the enhanced susceptibility of neonates to echovirus infections.\n\nSignificanceEchoviruses are associated with aseptic meningitis and induce severe disease, and even death, in neonates and young infants. Here, we identify the neonatal Fc receptor (FcRn) as a pan-echovirus receptor. FcRn is expressed on the surface of the human placenta, and throughout life in intestinal enterocytes, liver hepatocytes, and in the microvascular endothelial cells that line the blood-brain barrier. This pattern of expression is consistent with the organ sites targeted by echoviruses in humans, with the primary entry site of infection in the intestinal tract and subsequent infection of secondary tissues including the liver and brain. These findings provide important insights into echovirus pathogenesis and may explain the enhanced susceptibility of infants and neonates to echovirus-induced disease.

microbiology↗