Biology subjects

Yong, L.

Publications and source records attributed to Yong, L..

14 recordsLinked to original sources

bioRxiv2026

CXCR3 on transferred T cells enables vaccine-boosted adoptive T-cell therapy in solid tumors

Adoptive T-cell therapy (ACT) has demonstrated marked clinical benefit in hematological malignancies but has limited efficacy against solid tumors. Cancer vaccines can improve ACT, but the mechanisms underlying this combination are poorly understood. Here, we combined ACT with chimpanzee adenovirus ChAdOx1 (ChAd) and modified vaccinia Ankara (MVA) encoding tumor antigens. Whereas PD1 blockade failed to improve ACT, the combination with ChAd/MVA vaccination drove durable regression of established tumors, correlating with expansion of tumor-reactive T cells in lymphoid organs and increased tumor infiltration by T cells. Mechanistically, ChAd priming induced CXCR3 ligands (CXCL10 and CXCL9) in the vaccine-draining lymph node, thereby recruiting transferred T cells to this node independently of cognate antigen. CXCR3 expression on the transferred T cells, but not on host cells, was required for the anti-tumor effect of the combination therapy and favored T-cell accumulation in the vaccine-draining lymph node and the tumor. These findings identify CXCR3 on the transferred T cells as a determinant of ACT plus vaccination synergy and provide a rationale for combining viral-vector vaccines with TCR-T therapies, and for selecting or engineering T cells to retain CXCR3 expression.

immunology↗

bioRxiv2026

A spatiotemporal single-cell atlas reveals coordinated immune, metabolic, and nutrient exchange programs and a coumarin-centered metabolic switch during soybean arbusular mycorrhizal symbiosis

Arbuscular mycorrhizal fungi (AMF) establish intimate symbiosis with plant roots, yet the cell-type-specific regulatory and metabolic programs governing this interaction remain poorly resolved. Here, we integrate single-nucleus RNA sequencing (snRNA-seq) with spatial metabolomics across a temporal gradient of soybean root colonization (2-8 weeks post inoculation) to construct a high-resolution, multi-omic atlas of AMF symbiosis. Profiling 33,410 nuclei spanning all major root cell types, we uncover dynamic, cell-type-resolved transcriptional reprogramming coupled to spatially localized metabolite accumulation. Early colonization triggers a robust, epidermis-localized immune response alongside cortex-specific epigenetic reprogramming, mediated by RNA-directed DNA methylation machinery, suggesting active suppression of defense in fungal accommodation zones. Spatial metabolomics reveals a biphasic metabolic transition from flavonoid- and terpenoid-rich signaling states to lipid-dominated nutrient exchange, aligned with colonization progression. In parallel, coordinated carbon allocation and lipid biosynthesis pathways were activated in cortex and vascular tissues, supporting fungal dependence on host-derived fatty acids and sugars. Nutrient exchange programs, particularly nitrogen and phosphorus transport, exhibit strong pericycle and phloem specificity, highlighting systemic integration of symbiotic benefits. Through co-expression network analysis, we identify a previously uncharacterized coumarin-centered metabolic switch, governed by GmF6H1-2, that is essential for efficient colonization, as validated by natural loss-of-function variants. Collectively, this study provides a comprehensive, spatially resolved framework linking gene regulation, metabolism, and cell identity, revealing that AMF symbiosis is orchestrated through coordinated immune modulation, metabolic rewiring, and nutrient flux partitioning at single-cell resolution. Key pointsO_LIMulti-omic integration reveals cell-type-resolved symbiotic programs C_LIO_LISymbiosis requires spatially coordinated immune reprogramming C_LIO_LIA biphasic metabolic shift underpins colonization dynamics C_LIO_LICarbon and nutrient flux are partitioned across specialized cell types C_LIO_LIDiscovery of a coumarin-driven "metabolic GO-switch" controlling symbiosis C_LI

plant biology↗

bioRxiv2026

Evolutionary divergence and adaptive potential of scototaxis in juvenile Trinidadian Guppies

Habitat choice and resource acquisition represent an intrinsic trade-off, resulting in variation among individuals and potentially local adaptation among populations. Here, we quantify scototaxis, or preference for dark versus light backgrounds, in juvenile guppies. Scototaxis assays, in which individuals choose between safer dark and riskier light backgrounds, are widely used as a measure of boldness in small fishes, but they can equally be interpreted as choice between two habitats. By rearing and testing 586 fish descended from ten natural populations from Trinidad under common garden conditions, we first quantify (broad sense) heritable variation, i.e. evolutionary potential, within populations. Next, we test for evolutionary divergence among populations in mean preference, and if present, whether ancestral predation regime is a mediator of divergence. Finally, we ask whether families and/or populations differ in the amount of behavioural variation they contain. Preference varied among families (12% of total variance), consistent with broad-sense heritable variation. We also found that mean preference varied among populations (11% of total variance explained). Evolutionary divergence among-populations is partly explained by ancestral predation regime, with populations from low-predation sites showing a stronger preference for dark backgrounds than high-predation populations from the same river. Additionally, we find that within-population behavioural variation is greater in high-predation populations. We conclude that guppy populations contain heritable variation that could facilitate adaptive evolution if scototaxis is subject to natural selection. Furthermore, while genetic drift may also contribute to evolutionary divergence among-populations, observed patterns are qualitatively consistent with local adaption to predation regime. Our results suggests that high predation sites favour bolder habitat choice on average, but also that local predation regime shapes the evolutionary dynamics of variation, perhaps by maintaining shy-bold variation among individuals, or by favouring individuals with less-predictable behaviour.

evolutionary biology↗

bioRxiv2026

Bridge recombinase enables versatile rewriting of bacterial genomes

Bacteria drive crucial processes across ecosystems and impact human health, yet tools to rewrite microbiomes remain limited. Here, we show that bridge recombinase enables versatile and programmable genome editing across the bacterial tree of life. In Escherichia coli, we achieved 142 kb insertions at >90% efficiency, megabase-scale inversions (2.3 Mb), and pathway-scale 50 kb excisions. With a single ortholog and bridge RNA (bRNA), we edited bacterial isolates spanning five phyla and diverse members of two human gut communities. We overcame cross-reactivity between co-expressed bRNAs to establish search-and-replace Targetable Recombinase Assisted DNA Exchange (TRADE) editing and demonstrated capture and interphylum transfer of chromosomal pathways, enabling programmable horizontal gene transfer. These advances establish bridge recombinase as a foundation for reprogramming gene flow in complex microbial communities.

synthetic biology↗

bioRxiv2025

Prolactin links psychological stress to psoriasis via a fibroblast-chemokine pathway

Psoriasis is a chronic inflammatory skin disease that forms a vicious cycle with psychological stress. Whether and how the hypothalamic-pituitary (HP) axis-mediated neuroendocrine system regulates psoriasis remains obscure. Here, we report elevated levels of the pituitary hormone prolactin (PRL) in both psoriasis patients and imiquimod (IMQ)-induced psoriasis mice. Mechanistically, PRL acts on dermal PRLR-expressing fibroblasts to promote the production of the chemokines CCL2 and CCL7, which then recruit monocytes/macrophages into psoriatic lesional skin, thereby activating local IL-17A-producing T cells. Accordingly, pharmacological targeting of PRL signaling inhibits the recruitment of monocytes/macrophages, decreases the frequency of IL-17A-producing T cells, and alleviates IMQ-induced psoriasis in mice. In summary, our results delineate a mechanism by which the neuroendocrine hormone PRL aggravates psoriasis and highlight a potential therapeutic strategy of inhibiting PRL-PRLR signaling, particularly in psoriasis patients experiencing psychological stress.

immunology↗

bioRxiv2025

Isotemporal Substitution Effects of 24-hour Movement Behaviors on Executive Function in Preschool Children

ObjectiveThis study aims to examine the relationship between 24-h movement behaviors (MBs) and executive function (EF) in preschool children. MethodsA total of 266 preschool children participated in this study. Physical activity (PA) and sedentary behavior (SB) were measured using an accelerometer (ActiGraph GT3X-BT), sleep duration was assessed using sleep logs, and EF was evaluated using the Early Years Toolbox. Compositional data analysis was employed to explore associations among the three movement behaviors. Results(1) The relative distribution of 24-h MBs was significantly associated with inhibition, shifting, and updating (all p < 0.001), with a model explanatory power > 10%. The explanatory power was the highest for inhibition (16.3%). (2) After adjusting for other MBs, SB was negatively associated with inhibition ({gamma}12 = -0.11, p < 0.001), shifting ({gamma}12 = -1.45, p = 0.001), and updating ({gamma}12 = -0.58, p = 0.004). In contrast, sleep (SP) was positively associated with shifting ({gamma}11 = 1.60, p = 0.020). (3) When 15 min/day of SB was isotemporally substituted with SP, inhibition scores increased by 0.003, and shifting scores increased by 0.064; conversely, replacing SP with SB resulted in a significant decline. ConclusionThe relative distribution of 24-h MBs significantly predicted EF in preschool children. Among MBs, SB and SP were most strongly associated with EF. Shifting SB toward SP may effectively improve EF performance, particularly shifting ability.

developmental biology↗

bioRxiv2024

ADM: Adaptive Graph Diffusion for Meta-Dimension Reduction

Dimension reduction is ubiquitous in high dimensional data analysis. Divergent data characteristics have driven the development of various techniques in this field. Although individual techniques can capture specific aspects of data, they often struggle to grasp all the intricate and complex patterns and structures. To address this limitation, we introduce ADM (Adaptive graph Diffusion for Metadimension reduction), a novel meta-dimension reduction method grounded in graph diffusion theory. ADM integrates results from diverse dimension reduction techniques to leverage the unique strength of each individual technique. By employing dynamic Markov processes, ADM simulates information propagation for each dimension reduction result, thereby transforming traditional spatial measurements into dynamic diffusion distances. Importantly, ADM incorporates an adaptive mechanism to tailor the time scale of information diffusion according to sample-specific attributes. This improvement facilitates a more thorough exploration of the datasets overall structure and allows the heterogeneity among samples.

bioinformatics↗

bioRxiv2024

Identification of cell-type-specific response to silicon treatment in soybean leaves through single nucleus RNA-sequencing

In agriculture, mineral nutrients uptake and deposition profoundly influence plant development, stress resilience, and productivity. Despite its classification as a non-essential element, silicon (Si) is crucial in plant physiology, particularly in defense response and stress mitigation. While genetic and molecular mechanisms of Si uptake and transport are well-studied in monocots, particularly rice, its role in dicot species, such as soybean, remains unclear at the cellular and molecular levels. Traditional bulk transcriptomics methods lack the resolution to uncover cellular heterogeneity. Here, we present a study by utilizing single-nucleus RNA sequencing (snRNA-seq) to dissect cellular responses to Si accumulation in soybean leaves. Our analysis revealed distinct cellular populations, including a novel Si-induced cell cluster within vascular cells, suggesting a specific mechanism of Si distribution. Si treatment induced the expression of defense-related genes, particularly enriched in vascular cells, highlighting their specialized role in activating plant defense mechanisms. Moreover, Si modulated the expression of genes involved in RNA silencing, phytoalexin biosynthesis, and immune receptor signaling, suggesting a mechanism of transcriptional priming of genes involved in defense responses. We further investigated putative Si transporters, revealing differential expression patterns in response to Si treatment, suggesting presence of active and gradient-based transport mechanisms. Our findings shed light on the vital biotic stress regulatory networks governed by Si treatment in soybean leaves, paving potential strategies for enhancing stress tolerance and agronomic performance in crops.

plant biology↗

bioRxiv2022

Partial sex linkage and linkage disequilibrium on the guppy sex chromosome

The guppy Y chromosome has been considered a model system for the evolution of suppressed recombination between sex chromosomes, and it has been proposed that complete sex-linkage has evolved across about 3 Mb surrounding this fishs sex-determining locus, followed by recombination suppression across a further 7 Mb of the 23 Mb XY pair, forming younger "evolutionary strata". Sequences of the guppy genome show that Y is very similar to the X chromosome, making it important to understand which parts of the Y are completely non-recombining, and whether there is indeed a large completely non-recombining region. Here, we describe new evidence that supports a different interpretation of the data that suggested the presence of such a region. We analysed PoolSeq data in samples from multiple natural populations from Trinidad. This yields evidence for linkage disequilibrium (LD) between sequence variants and the sex-determining locus. Downstream populations have higher diversity than upstream ones (which display the expected signs of bottlenecks). The associations we observe conform to predictions for a genome region with infrequent recombination that carries one or more sexually antagonistic polymorphisms. They also suggest the region in which the sex-determining locus must be located. However, no consistently male-specific variants were found, supporting the suggestion that any completely sex-linked region may be very small.

evolutionary biology↗

bioRxiv2020

Sensory-based quantification of male colour patterns in Trinidadian guppies reveals nonparallel phenotypic evolution across an ecological transition in multivariate trait space

Parallel evolution, in which independent populations evolve along similar phenotypic trajectories, offers insights into the repeatability of adaptive evolution. Here, we revisit a classic example of parallelism, that of repeated evolution of brighter males in the Trinidadian guppy. In guppies, colonisation of low predation habitats is associated with emergence of more colourful phenotypes since predator-induced viability selection for crypsis weakens while sexual selection by female preference for conspicuity remains strong. Our study differs from previous investigations in three respects. First, we adopt a multivariate phenotyping approach to characterise parallelism in multi-trait space. Second, we use ecologically-relevant colour traits defined by the visual systems of the two selective agents (i.e. guppy, predatory cichlid). Third, we estimate population genetic structure to test for adaptive (parallel) evolution against a model of neutral phenotypyc divergence. We find strong phenotypic differentiation that is inconsistent with a neutral model, but only limited support for the predicted pattern of greater conspicuity at low predation. Effects of predation regime on each trait were in the expected direction, but weak, largely non-significant, and explained little among-population variation. In multi-trait space, phenotypic trajectories of lineages colonising low from high predation regimes were not parallel. Our results are consistent with reduced predation risk facilitating adaptive differentiation by female choice, but suggest that this proceeds in (effectively) independent directions of multi-trait space across lineages. Pool-sequencing data also revealed SNPs showing greater differentiation than expected under neutrality and/or associations with known colour genes in other species, presenting opportunities for future genetic study.

evolutionary biology↗

bioRxiv2020

Using GC content to compare recombination patterns on the sex chromosomes and autosomes of the guppy, Poecilia reticulata, and its close outgroup species

Summary/AbstractGenetic and physical mapping of the guppy (P. reticulata) have shown that recombination patterns differ greatly between males and females. Crossover events occur evenly across the chromosomes in females, but in male meiosis they are restricted to the tip furthest from the centromere of each chromosome, creating very high recombination rates per megabase, similar to the high rates in mammalian sex chromosomes pseudo-autosomal regions (PARs). We here used the intronic GC content to indirectly infer the recombination patterns on guppy chromosomes. This is based on evidence that recombination is associated with GC-biased gene conversion, so that genome regions with high recombination rates should be detectable by high GC content. Using intron sequences, which are likely to be under weak selection, we show that almost all guppy chromosomes, including the sex chromosome (LG12) have very high GC values near their assembly ends, suggesting high recombination rates due to strong crossover localisation in male meiosis. Our test does not suggest that the guppy XY pair has stronger crossover localisation than the autosomes, or than the homologous chromosome in a closely related fish, the platyfish (Xiphophorus maculatus). We therefore conclude that the guppy XY pair has not recently undergone an evolutionary change to a different recombination pattern, or reduced its crossover rate, but that the guppy evolved Y-linkage due to acquiring a male-determining factor that also conferred the male crossover pattern. The results also identify the centromere ends of guppy chromosomes, which were not determined in the guppy genome assembly.

evolutionary biology↗

bioRxiv2020

Locating the sex determining region of linkage group 12 of guppy (Poecilia reticulata)

We describe new genetic mapping results from 6 full-sib families in the guppy (Poecilia reticulata), two of which included recombinants between the X and Y chromosomes. These recombinants confirm that the guppy sex-determining locus is in the region identified by all previous studies, including a recent report suggesting a candidate sex-determining gene in this fish, close to the pseudo-autosomal region (or PAR) at the chromosome terminus. Our results suggest the presence of some errors in the current assembly of the guppy genome. In males, crossing over occurs at a very high rate in the PAR, and our genetic map of the region allows us to correct the marker order. We also identified two unplaced scaffolds carrying genes that map to the PAR. Genetic mapping cannot be used to order markers in the region where crossing over is infrequent. However, our recombinant male is informative about the order, under the reasonable assumption that crossovers are infrequent. Our mapping families and natural population samples also show that the recently proposed candidate for this species sex-determining gene is not completely sex-linked. We detect an association between individuals sex and an SNP in the sex-determining region, but not with a marker 0.9 Mb away from it, suggesting that variants in this region may be in linkage disequilibrium with the actual sex-determining factor, but that the factor itself has not yet been identified. So far, no consistently male-specific variant has been identified in the guppy sex-determining region.

genetics↗

bioRxiv2018

B1a cells protect against Schistosoma japonicum-induced liver inflammation and fibrosis by controlling monocyte infiltration

During Schistosoma infection, lack of B cells results in more severe granulomas, inflammation, and fibrosis in the liver, but the mechanisms underlying this pathology remain unclear. Thus, our aim was to clarify the mechanisms underpinning the immunomodulation of B cells in mice infected with Schistosoma japonicum. We found that B cell deficiency led to aggravated liver pathology, as demonstrated by increases in the size of the egg-associated granulomas, alanine transaminase levels, and collagen deposition. Compared with infected wild-type mice, infected B cell-deficient MT mice showed increased infiltration of Ly6Chi monocytes and higher levels of proinflammatory cytokines (tumor necrosis factor alpha, interleukin 6, and interleukin 12) and chemokines ([C-C motif] ligands (CCL)2, CCL3, CCL4, and CCL5). The results of flow cytometric analysis and cell transfer experiments showed that B1a cells increased significantly in the liver following S. japonicum infection, with some of those cells deriving from the peritoneal cavity. We also found that secretion of IL-10 from hepatic B cells increased significantly in infected wild-type mice and that this IL-10 was mainly derived from B1a cells. In addition, adoptively transferring peritoneal cavity B cells purified from wild-type, but not from IL-10-deficient mice, to MT mice significantly reduced liver pathology and liver infiltration of Ly6Chi monocytes. These reductions were accompanied by decreases in the expression levels of chemokines and inflammatory cytokines. Taken together, these data indicated that after S. japonicum infection, an increased number of hepatic B1a cells secrete IL-10, which inhibits the expression of chemokines and cytokines and suppresses the infiltration of Ly6Chi monocytes into the liver thereby alleviating liver early inflammation and late fibrosis. Understanding this immunomodulatory role of B1a cells in schistosomiasis may lead to the development of therapeutic strategies for Schistosoma-induced liver disease.\n\nAuthor summaryInfection with Schistosoma, a waterborne parasitic flatworm (trematode) commonly called a blood fluke, results in strong granulomatous inflammation caused by the deposition of eggs in the liver. A granuloma is a substantial immune cell infiltration around the eggs intermixed with liver cells that can protect the host against liver damage. However, excessive infiltration and inflammation can lead to severe liver injury and fibrosis. Here, we found that B1a cells accumulate in the liver of mice after S. japonicum-induced infection and that these B1a cells release the anti-inflammatory cytokine interleukin 10 to regulate inflammation. The B1a cell-derived interleukin 10 inhibits the expression of chemokines (which attract cells such as monocytes to sites of infection or inflammation) and thus restrains excessive infiltration of Ly6Chi monocytes (which may have proinflammatory activity) into the liver, thereby alleviating early inflammation and later fibrosis. Our study provides insight into the immunomodulation of B1a cells in schistosomiasis and offers key information for the development of therapeutic strategies in Schistosoma-induced liver disease.

immunology↗

bioRxiv2018

Sexually dimorphic recombination can facilitate the establishment of sexually antagonistic polymorphisms in guppies

Summary/AbstractRecombination suppression between sex chromosomes is often stated to evolve in response to polymorphisms for mutations that affect fitness of males and females in opposite directions (sexually antagonistic, or SA, mutations), but direct empirical support is lacking. The sex chromosomes of the fish Poecilia reticulata (the guppy) carry SA polymorphisms, making them excellent for testing this hypothesis for the evolution of sex linkage. We resequenced genomes of male and female guppies and, unexpectedly, found that variants on the sex chromosome indicate no extensive region with fully sex-linked genotypes, though many variants show strong evidence for partial sex linkage. We present genetic mapping results that help understand the evolution of the guppy sex chromosome pair. We find very different distributions of crossing over in the two sexes, with recombination events in male meiosis detected only at the tips of the chromosomes. The guppy may exemplify a route for sex chromosome evolution in which low recombination in males, likely evolved in a common ancestor, has facilitated the establishment of sexually antagonistic polymorphisms.

evolutionary biology↗