Biology subjects

Miller, S. E.

Publications and source records attributed to Miller, S. E..

At least 19 recordsLinked to original sources

bioRxiv2026

Large scale application of species distribution models to predict future vulnerability to social wasp invasions

Social wasps (family: Vespidae) are increasingly concerning invaders and have been subject to increased detections and a growing number of invasive populations in the last few decades. As established invasive populations are challenging to eradicate, preventing introductions and prioritizing early interventions are the most cost-effective management solutions to mitigate these effects. A current challenge to this approach is that species distribution data is limited for many social wasp species, hindering our ability to accurately predict novel habitats with high suitability. To address this gap, we used MAXENT to create species distribution models (SDM) for 299 species of social vespid. We identified existing invasive populations of social wasps and incorporated their current invasive ranges to improve the transferability of our models in predicting habitat suitability in new environments. Current range sizes and habitat suitability varied widely among species and genera. We identified new species of high invasive concern, particularly in the genus Vespa. We also identified previously unrecognized regions that may be at high risk of future invasion primarily in Central Africa and the Indo-Australian Archipelago. Combining current and suitable ranges, we calculated an "Invasion Risk Score" to compare the relative likelihood of each species establishing a new invasive population based upon habitat suitability. To assess invasion risk in the future, we projected habitat suitability under four Shared Socioeconomic Pathway (SSP) climate change scenarios. Under all scenarios, species faced significant changes in habitat suitability for current native ranges. Habitat suitability generally shrank and shifted towards the poles, leaving equatorial species at highest risk of habitat loss. Notably, Vespa was the only genus whose suitable habitat expanded under these climate scenarios. Our framework demonstrates how multi-species SDMs can be applied to risk management of invasive populations.

ecology↗

bioRxiv2026

Quantitative profiling of intrinsic dCas9-DNA recognition reveals key determinants of guide RNA performance

CRISPR technologies based on nuclease-deactivated Cas9 (dCas9) rely on programmable DNA binding rather than DNA cleavage, yet the intrinsic DNA-recognition properties that govern optimal guide RNA (gRNA) performance remain poorly understood. Existing approaches either measure genomic occupancy in cells or infer dCas9 behavior from cleavage-based Cas9 datasets, despite DNA binding being substantially more permissive than DNA cleavage. Here we introduce TANGO (Targeted Array-based Nucleic acid-Guided Occupancy), a high-density DNA-array platform that quantitatively profiles intrinsic dCas9:gRNA binding across tens of thousands of DNA targets in a cell-free system. TANGO captures established features of dCas9 target recognition, while providing substantially greater sensitivity than prior assays. Comparison with ChIP-seq data demonstrates that intrinsic DNA-binding specificity is a major driver of genomic occupancy and reveals that chromatin accessibility modulates the intrinsic binding affinity required for dCas9 recruitment. Across CRISPRi/a guides, TANGO identifies multiple independent biochemical determinants of guide performance--including on-target affinity, mismatch tolerance, and ribonucleoprotein assembly--and flags problematic and highly promiscuous guides overlooked by current specificity metrics. Unexpectedly, some guides retain substantial guide-directed DNA binding even in the absence of a protospacer-adjacent motif (PAM), revealing an additional dimension of dCas9 specificity. Together, these results establish intrinsic DNA recognition as a quantitative and experimentally accessible determinant of dCas9 function, providing a framework for improving guide selection and enhancing the precision of CRISPR technologies.

genomics↗

bioRxiv2026

Spatial turnover amplifies with trophic level in hyperdiverse food webs

One of the most intuitive ideas in ecology is that diversity at lower trophic levels in food webs provides niches to support diversity at higher trophic levels. This accumulation of diversity can be limited by survival of species in the landscape, but revealing these limits has been challenging. We analyze spatial turnover in a hyperdiverse parasitoid-caterpillar-plant food web across 75,000 km2 of continuous lowland rainforest in Papua New Guinea. Species turnover across sites is higher in parasitoids than in their caterpillar hosts. Furthermore, turnover of interactions is also higher in parasitoid-caterpillar than caterpillar-plant networks. Spatial turnover thus amplifies upwards across trophic levels, forcing parasitoids to live closer to spatial persistence limits. Consequently, progressing rainforest fragmentation can especially endanger parasitoids.

ecology↗

bioRxiv2026

Mismatch tolerance of a gRNA for CRISPR-based gene activation confers broad activity critical for cell reprogramming

CRISPR activation and interference systems (CRISPRa/i) are widely used for programmable transcriptional control. Although these technologies are capable of highly specific single-gene activity, some applications of transcriptional network reprogramming require broad, genome-wide effects. Here, we identify a CRISPRa gRNA that robustly reprograms astrocyte transcriptional state. Unexpectedly, this activity arises from extensive off-target binding that induces expression changes in thousands of genes, unlike neighboring gRNAs targeting the same intended on-target site. We leverage this promiscuous gRNA to dissect determinants of gRNA-driven off-target dCas9 binding in the context of transcriptional reprogramming. Using ChIP-seq, high-throughput protein-binding microarrays, and gRNA-variant library screening in cells, we demonstrate that PAM-proximal bases are primary determinants of genomic binding, mismatch tolerance is both gRNA- and base-specific, and targeted mutations within the PAM-proximal region can tune gRNA specificity. We further demonstrate that CRISPRa-driven phenotypes can reflect combined contributions from widespread off-target activity and dose-dependent on-target effects. These findings highlight the potentially widespread impacts of CRISPRa off-target activity, underscore the need to account for cryptic effects when selecting and evaluating gRNAs for programming cell phenotypes, and demonstrate that multi-site binding by CRISPRa systems can be exploited as a feature for network-level perturbations in cell reprogramming. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/703129v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@b697b0org.highwire.dtl.DTLVardef@1a0b390org.highwire.dtl.DTLVardef@16ce710org.highwire.dtl.DTLVardef@b5d87a_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2025

Characterization of Phytoplankton-Excreted Metabolites Mediating Carbon Flux through the Surface Ocean

The marine labile dissolved organic carbon (DOC) pool is a dynamic reservoir of thousands of molecules that cycles approximately one-quarter of Earths primary production within days to weeks. After excretion by phytoplankton and other microbes, metabolites are rapidly consumed, resulting in low standing concentrations (picomolar to low nanomolar). Despite the decades-long search for labile DOC sources and molecular identities, marine phytoplankton exometabolomes are not well characterized, largely due to difficulties in measuring small polar molecules in saline water. Here, we profiled the exometabolomes of six axenic phytoplankton species representing key functional groups including a diatom (Thalassiosira pseudonana CCMP1335), a picoeukaryote (Micromonas commoda RCC299), a coccolithophore (Gephyrocapsa huxleyi CCMP371), a diazotrophic cyanobacterium (Crocosphaera watsonii WH8501), and two picocyanobacteria (Prochlorococcus marinus MIT 9301 and Synechococcus WH8102). From these cultures, we quantified 56 amine- and alcohol-containing exometabolites representing 11 compound classes which in sum comprised up to 23.4% of phytoplankton-excreted DOC. We estimated that these phytoplankton-derived exometabolites could supply up to 5% of the daily carbon quota of the dominant heterotrophic bacterium SAR11 in the surface ocean. Substantial variations in exometabolite identity and concentration across phytoplankton taxa underscore taxonomic diversity as a key driver in the supply and composition of labile DOC. This taxonomic variation predicts geographic and seasonal differences in the distribution of marine dissolved metabolites that underpin the cycling of labile DOC back to CO2. Overall, our work suggests that phytoplankton exometabolites are key chemical currencies that mediate significant carbon fluxes within the oceans carbon cycle. Significance StatementPhytoplankton exometabolites are key components of the marine labile dissolved organic carbon (DOC) pool, which drives major a fraction of the oceanic carbon flux. Yet, their composition and flux are poorly constrained. Leveraging new methods, we quantified amine- and alcohol-containing exometabolites in diverse phytoplankton and found they varied taxonomically. These exometabolites accounted for up to 23.4% of excreted DOC, potentially supporting a sizable fraction of the global heterotrophic growth. Integrating our results with ecological models suggest that exometabolite composition varies geographically and seasonally in response to changing phytoplankton community structures. Our findings illuminate the long-standing "black box" of labile DOC and link taxonomic diversity to the chemical currencies underpinning the microbe-metabolite networks at the heart of the marine carbon cycle.

ecology↗

bioRxiv2025

Comprehensive profiling of transcription factors for reprogramming human astrocytes to neuronal cells through endogenous CRISPR-based gene activation

Neuronal loss is a hallmark of neurodegeneration and brain injury. Direct reprogramming of astrocytes into neurons has emerged as a promising approach to restore lost neurons. Comprehensive mapping and characterization of candidate astrocyte-to-neuron reprogramming factors is an essential step to realizing the potential of this strategy. Here, we established a CRISPR activation (CRISPRa)-based approach for neuronal reprogramming of primary human astrocytes. We conducted high-throughput CRISPRa screens of all human genes encoding transcription factors (TFs) to identify novel and efficient reprogramming factors. scRNA-seq characterization of top hits revealed that single TFs reprogram primary human astrocytes into multiple neuronal subtypes with distinct cell type-specific gene signatures. We demonstrate that INSM1 reprograms astrocytes to a glutamatergic neuron-like state and has broad neurogenic activity across different cell types and across human and mouse contexts. Finally, we conduct paired CRISPRa screens to identify cofactors that cooperate with INSM1 to enhance neuronal reprogramming and subtype specification, and elucidate genomic mechanisms of interaction and downstream regulators.

cell biology↗

bioRxiv2025

A high-resolution diel survey of surface ocean metagenomes, metatranscriptomes, and transfer RNA transcripts

The roles of marine microbes in ecosystem processes are inherently linked to their ability to sense, respond, and ultimately adapt to environmental change. Capturing the nuances of this perpetual dialogue and its long-term implications requires insight into the subtle drivers of microbial responses to environmental change that are most accessible at the shortest scales of time. Here, we present a multi-omics dataset comprising surface ocean metagenomes, metatranscriptomes, tRNA transcripts, and biogeochemical measurements, collected every 1.5 hours for 48 hours at two stations within coastal and adjacent offshore waters of the tropical Pacific Ocean. We expect that this integrated dataset of multiple sequence types and environmental parameters will facilitate novel insights into microbial ecology, microbial physiology, and ocean biogeochemistry and help investigate the different mechanisms of adaptation that drive microbial responses to environmental change.

microbiology↗

bioRxiv2025

Ribosomal protein phylogeography offers quantitative insights into the efficacy of genome-resolved surveys of microbial communities

The increasing availability of microbial genomes is essential to gain insights into microbial ecology and evolution that can propel biotechnological and biomedical advances. Recent advances in genome recovery have significantly expanded the catalogue of microbial genomes from diverse habitats. However, the ability to explain how well a set of genomes account for the diversity in a given environment remains challenging for individual studies or biome-specific databases. Here we present EcoPhylo, a computational workflow to characterize the phylogeography of any gene family through integrated analyses of genomes and metagenomes, and apply this approach to ribosomal proteins to quantify phylogeny-aware genome recovery rates in two genome-resolved investigations of the human gut and oral cavity. Our results demonstrate that EcoPhylo reveals highly resolved, reference-free, multi-domain phylogenies in conjunction with distribution patterns of individual clades across environments, providing a means to assess genome recovery in individual studies and benchmark genome collections.

microbiology↗

bioRxiv2024

Adaptive adjustment of significance thresholds produces large gains in microbial gene annotations and metabolic insights

Gene function annotations enable microbial ecologists to make inferences about metabolic potential from genomes and metagenomes. However, even tools that use the same database and general approach can differ markedly in the annotations they recover. We compare three popular methods for identifying KEGG Orthologs, applying them to genomes drawn from a range of bacterial families that occupy different host-associated and free-living biomes. Our results show that by adaptively tuning sequence similarity thresholds, sensitivity can be substantially improved while maintaining accuracy. We observe the largest improvements when few reference sequences exist for a given protein family, and when annotating genomes from non-model organisms (such as gut-dwelling Lachnospiraceae). Our results suggest that straightforward heuristic adjustments can broadly improve microbial metabolic predictions.

bioinformatics↗

bioRxiv2023

Adaptive genomic variation is linked to a climatic gradient in a social wasp

Species vary in their ability to adapt to rapid changes, with the presence of genetic variation often facilitating long-term evolutionary responses. Given the impending threat of climate change, it is critical to investigate how genetic variation facilitates persistence and possible range expansion in animals. Here, we combine genomic and climatic data to characterize the drivers of local adaptation in the widely distributed, social wasp Mischocyttarus mexicanus cubicola. Using whole genome sequence data, we show that adaptive genomic variation is linked to a climatic gradient across the broad distribution of this species. We found strong population structure, dividing the species into two genetic clusters that follow subtropical and temperate regions. Patterns of gene flow across the range deviate from those expected by isolation by distance alone with climatic differences resulting in reduced gene flow even between adjacent populations. Importantly, genotype-environment analyses reveal candidate single nucleotide polymorphism (SNPs) associated with temperature and rainfall, suggesting adaptation for thermal and desiccation tolerance. In particular, candidate SNPs in or near mitochondrial genes ND5, CO1, and COIII are linked to cold tolerance and metabolism. Similarly, the Gld nuclear gene shown to mediate cold hardiness and cuticle formation, shows two candidate SNPs with non-synonymous mutations unique to temperate populations. Together, our results reveal candidate SNPs consistent with local adaptation to distinct climatic conditions. Thus, the integration of genomic and climatic data can be a powerful approach to predict vulnerability and persistence of species under rapid climate change.

evolutionary biology↗

bioRxiv2023

Hiding in Plain Sight: Phylogenomics Reveals a New Branch on the Noctuoidea Tree of Life

We present the results of the first phylogenomic analyses based on anchored hybrid enrichment (AHE) data from densely sampled tribes and subfamilies of Notodontidae (Prominent Moths). Our analyses reveal the familys polyphyly with respect to an assemblage of genera related to Scrancia Holland that has been variously recognized at the tribal or subfamilial rank. We propose and re-describe Scranciidae, stat. nov., and recognize 21 genera and approximately 100 species--distributed in Africa, Asia, and Australia and not represented in previous phylogenomic studies--from the six recognized noctuoid families (Noctuidae, Erebidae, Euteliidae, Nolidae, Notodontidae, and Oenosandridae). We further re-interpret morphological synapomorphies previously proposed for Notodontidae (including Scranciidae) and for the trifid Noctuoidea, viz. the ventral-facing tympanum and trifid forewing venation-- characters previously called into question when Doidae were transferred from Noctuoidea to Drepanoidea. Deep-level relationships within Noctuoidea are not firmly established outside the clade comprising the four quadrifid families (Noctuidae, Erebidae, Euteliidae, and Nolidae), and in attempting to establish the phylogenetic position of Scranciidae relative to Notodontidae, Oenosandridae, and the quadrifids, we obtain conflicting results depending on data type (amino acid vs. nucleotide) and analytical framework (maximum likelihood, multi-species coalescent, and parsimony). We also demonstrate that discordant topologies among these ancient lineages yield drastically different divergence time estimates, highlighting the need for caution when interpreting phylogenetic dating of uncertain topologies. Following multiple analyses of several datasets designed around the distribution of missing data, and an evaluation of strict support measures at the deepest nodes of the noctuoid tree, we provisionally conclude that this ambiguity is a function of character conflict amplified by missing data and short branch lengths, and that in the topology best supported by the available data, Scranciidae is placed well outside Notodontidae and sister to the remaining Noctuoidea.

evolutionary biology↗

bioRxiv2022

Evolutionary history of Euteliidae (Lepidoptera, Noctuoidea)

The Euteliidae stand apart in the Noctuoidea as the second smallest family, but most highly specialized in terms of larval hostplant relationships, favouring plant families with high levels of resin or latex, including the family dominant in Oriental lowland forests, the Dipterocarpaceae. Given the proportionally large foliage biomass represented by dipterocarps, exploitation of this abundant resource by lepidopteran defoliators is surprisingly low, and the Euteliidae may have achieved this through pre-adaption to dipterocarp chemical defences. Therefore, to assess this, we performed a molecular phylogenetic analysis on the family Euteliidae to clarify deep divergences and elucidate evolutionary relationships at the level of the subfamily, tribe, and genus. Our dataset consists of 6.3 kbp of one mitochondrial and seven nuclear DNA loci and was analyzed using model-based phylogenetic methods, i.e., maximum likelihood and Bayesian inference. We attempted to diagnose apomorphic morphological character states for Euteliidae and each monophyletic group within the family. Additionally, the evolution of hostplant use was reconstructed and a molecular-dating approach was conducted to assess the ages of major lineages within Euteliidae. We present an updated phylogenetic hypothesis for Euteliidae consisting of two strongly supported subfamilies: Euteliinae and Stictopterinae. Within Stictopterinae there are two tribes: Stictopterini and Odontodini. Several genera (e.g., Targalla, Paectes, Marathyssa, Eutelia) were found to be polyphyletic and require taxonomic revision. Two new genera (Niklastelia and Pellinentelia) are described and several taxonomic changes (e.g., new combinations and new synonymies) are made. The Neotropical genus Thyriodes, currently included in Euteliidae, is found to be associated with Erebinae (Erebidae). The divergence time estimate for the split between the Euteliidae and Noctuidae is at 53 my, and the Euteliidae split into the subfamilies Euteliinae and Stictopterinae at 42 my. In Stictopterinae, the tribes Stictopterini and Odontodini split at 31 my and the Euteliinae began a much more complex diversification at 34 my. Ancestral hostplant reconstruction identified Malpighiales (e.g., Clusiaceae) as the ancestral larval hostplant order for the family Euteliidae. The ancestors of Stictopterinae also appear to have been Malpighiales feeders, but then split into exclusive specialisms on Malvales (Odontodini) and Malpighiales (Stictopterini) hostplants. Larvae of Stictopterini appear to be restricted to Clusiaceae, apart from a few records from Dipterocarpaceae. In Euteliinae, Anacardiaceae are predominant as larval hosts. Thus, all hosts in the family are lactiferous, possibly providing some degree of pre-adaptation for exploiting Dipterocarpaceae.

evolutionary biology↗

bioRxiv2022

Structure-informed microbial population genetics elucidate selective pressures that shape protein evolution

Comprehensive sampling of natural genetic diversity with metagenomics enables highly resolved insights into the interplay between ecology and evolution. However, intra-population genomic variation represents the outcome of both stochastic and selective forces, making it difficult to identify whether variants are maintained by adaptive, neutral, or purifying processes. This is partly due to the reliance on gene sequences to interpret variants, which disregards the physical properties of three-dimensional gene products that define the functional landscape on which selection acts. Here we describe an approach to analyze genetic variation in the context of predicted protein structures, and apply it to study a marine microbial population within the SAR11 subclade 1a.3.V, which dominates low-latitude surface oceans. Our analyses reveal a tight association between the patterns of nonsynonymous polymorphism, selective pressures, and structural properties of proteins such as per-site relative solvent accessibility and distance to ligands, which explain up to 59% of genetic variance in some genes. In glutamine synthetase, a central gene in nitrogen metabolism, we observe decreased occurrence of nonsynonymous variants from ligand binding sites as a function of nitrate concentrations in the environment, revealing genetic targets of distinct evolutionary pressures maintained by nutrient availability. Our data also reveals that rare codons are purified from ligand binding sites when genes are under high selection, demonstrating the utility of structure-aware analyses to study the variants that likely impact translational processes. Overall, our work yields insights into the governing principles of evolution that shape the genetic diversity landscape within a globally abundant population, and makes available a software framework for structure-aware investigations of microbial population genetics. SignificanceIncreasing availability of metagenomes offers new opportunities to study evolution, but the equal treatment of all variants limits insights into drivers of sequence diversity. By capitalizing on recent advances in protein structure prediction capabilities, our study examines subtle evolutionary dynamics of a microbial population that dominates surface oceans through the lens of structural biology. We demonstrate the utility of structure-informed metrics to understand the distribution of nonsynonymous polymorphism, establish insights into the impact of changing nutrient availability on protein evolution, and show that even synonymous variants are scrutinized strictly to maximize translational efficiency when selection is high. Overall, our work illustrates new opportunities for discovery at the intersection between metagenomics and structural bioinformatics, and offers an interactive and scalable software platform to visualize and analyze genetic variants in the context of predicted protein structures and ligand-binding sites.

microbiology↗

bioRxiv2021

Evidence for a selective link between cooperation and individual recognition

The ability to recognize and discriminate among others is a frequent assumption of models of the evolution of cooperative behavior. At the same time, cooperative behavior has been proposed as a selective agent favoring the evolution of individual recognition abilities. While theory predicts that recognition and cooperation may co-evolve, data linking recognition abilities and cooperative behavior with fitness or evidence of selection are elusive. Here, we provide evidence of a fitness link between individual recognition and cooperation in the paper wasp Polistes fuscatus. Nest founding females in northern populations frequently form cooperative multiple foundress nests and possess highly variable facial patterns that mediate individual recognition. We describe a dearth of cooperative nesting, low phenotypic diversity, and a lack of individual recognition in southern populations. In a common garden experiment, northern co-foundress associations successfully reared offspring while all cooperative southern groups failed to rear any offspring, suggesting a fitness link between individual recognition and successful cooperation. Consistent with a selective link between individual recognition and cooperation, we find that rates of cooperative co-nesting correlate with identity-signaling color pattern diversity across the species range. Moreover, genomic evidence of recent positive selection on cognition loci likely to mediate individual recognition is substantially stronger in northern compared to southern P. fuscatus populations. Collectively, these data suggest that individual recognition and cooperative nesting behavior have co-evolved in P. fuscatus because recognition helps mediate conflict among co-nesting foundresses. This work provides evidence of a specific cognitive phenotype under selection because of social interactions, supporting the idea that social behavior can be a key driver of cognitive evolution.

animal behavior and cognition↗

bioRxiv2021

Sex differences in deleterious genetic variants in a haplodiploid social insect

Deleterious variants are selected against but can linger in populations at low frequencies for long periods of time, decreasing fitness and contributing to disease burden in humans and other species. Deleterious variants occur at low frequency but distinguishing deleterious variants from low frequency neutral variation is challenging based on population genetics data. As a result, we have little sense of the number and identity of deleterious variants in wild populations. For haplodiploid species, it has been hypothesized that deleterious alleles will be directly exposed to selection in haploid males, but selection can be masked in diploid females due to partial or complete dominance, resulting in more efficient purging of deleterious mutations in males. Therefore, comparisons of the differences between haploid and diploid genomes from the same population may be a useful method for inferring rare deleterious variants. This study provides the first formal test of this hypothesis. Using wild populations of Northern paper wasps (Polistes fuscatus), we find that males have fewer overall variants, and specifically fewer missense and nonsense variants, than females from the same population. Allele frequency differences are especially pronounced for rare missense and nonsense mutations and these differences lead to a lower genetic load in males than females. Based on these data we estimate that a large number of highly deleterious mutations are segregating in the paper wasp population. Stronger selection against deleterious alleles in haploid males may have implications for adaptation in other haplodiploid insects and provides evidence that wild populations harbor abundant deleterious variants.

evolutionary biology↗

bioRxiv2021

Lipid and nucleocapsid N-protein accumulation in COVID-19 patient lung and infected cells

The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global outbreak and prompted an enormous research effort. Still, the subcellular localization of the corona virus in lungs of COVID-19 patients is not well understood. Here, the localization of the SARS-CoV-2 proteins is studied in postmortem lung material of COVID-19 patients and in SARS- CoV-2 infected Vero cells, processed identically. Correlative light and electron microscopy on semi- thick cryo-sections, demonstrated induction of electron-lucent, lipid filled compartments after SARS- CoV-2 infection in both lung and cell cultures. In lung tissue, the non-structural protein 4 and the stable nucleocapsid N-protein, were detected on these novel lipid filled compartments. The induction of such lipid filled compartments and the localization of the viral proteins in lung of patients with fatal COVID-19, may explain the extensive inflammatory response and provide a new hallmark for SARS- Cov-2 infection at the final, fatal stage of infection.

microbiology↗

bioRxiv2021

Impact of isolation method on cellular activation and presence of specific tendon cell subpopulations during in vitro culture

Tendon injuries are common and heal poorly, due in part to a lack of understanding of fundamental tendon cell biology. A major impediment to the study of tendon cells is the absence of robust, well-characterized in vitro models. Unlike other tissue systems, current tendon cell models do not account for how differences in isolation methodology may affect the activation state of tendon cells or the presence of various tendon cell sub-populations. The objective of this study was to characterize how common isolation methods affect the behavior, fate, and lineage composition of tendon cell cultures. Tendon cells isolated by explant exhibited reduced proliferative capacity, decreased expression of tendon marker genes, and increased expression of genes associated with fibroblast activation compared to digested cells. Consistently, explanted cells also displayed an increased propensity to differentiate to myofibroblasts compared to digested cells. Explanted cultures from multiple different tendons were substantially enriched for the presence of scleraxis-lineage (Scx-lin+) cells compared to digested cultures, while the overall percentage of S100a4-lineage (S100a4-lin+) cells was dependent on both isolation method and tendon of origin. Neither isolation method preserved the ratios of Scx-lin+ or S100a4-lin+ to non-lineage cells seen in tendons in vivo. Combined, these data indicate that further refinement of in vitro cultures models is required in order to more accurately understand the effects of various stimuli on tendon cell behavior. Statement of clinical significanceThe development of informed in vitro tendon cell models will facilitate enhanced screening of potential therapeutic candidates to improve tendon healing.

cell biology↗

bioRxiv2021

Dynamic neurogenomic responses to social interactions and dominance outcomes in female paper wasps

Social interactions have large effects on individual physiology and fitness. In the immediate sense, social stimuli are often highly salient and engaging. Over longer time scales, competitive interactions often lead to distinct social ranks and differences in physiology and behavior. Understanding how initial responses lead to longer-term effects of social interactions requires examining the changes in responses over time. Here we examined the effects of social interactions on transcriptomic signatures at two points, at the end of a 45-minute interaction and 4 hours later, in female Polistes fuscatus paper wasp foundresses. Female P. fuscatus have variable facial patterns that are used for visual individual recognition, so we separately examined the transcriptional dynamics in the optic lobe and the central brain. Results demonstrate much stronger transcriptional responses to social interactions in the central brain compared to the optic lobe. Differentially regulated genes in response to social interactions are enriched for memory-related transcripts. Comparisons between winners and losers of the encounters revealed similar overall transcriptional profiles at the end of an interaction, which significantly diverged over the course of 4 hours, with losers showing changes in expression levels of genes associated with aggression and reproduction in paper wasps. On nests, subordinate foundresses are less aggressive, do more foraging and lay fewer eggs compared to dominant foundresses and we find losers shift expression of many genes, including vitellogenin, related to aggression, worker behavior, and reproduction within hours of losing an encounter. These results highlight the early neurogenomic changes that likely contribute to behavioral and physiological effects of social status changes in a social insect.

genomics↗