Biology subjects

Luo, M.

Publications and source records attributed to Luo, M..

At least 19 recordsLinked to original sources

bioRxiv2026

When does heterogeneity average out in coarse-grained ecological communities?

Ecological coarse-graining of individuals or species into aggregate variables, such as total biomass or regional abundance, is common practice, yet differences among species can still influence aggregate dynamics. We propose a metric for quantifying this irreducible dynamical heterogeneity. For small fluctuations near a stable equilibrium, we compare the aggregate fluctuation spectrum of the full dynamical system with that of the best Ornstein-Uhlenbeck model having the same dimension as the aggregate. The remaining spectral mismatch quantifies the dynamical effects of hidden differences that the fitted aggregate model cannot capture. For weakly interacting random community models at fixed collective interaction strength, we show that increasing species richness can either reduce or increase this heterogeneity, depending on how species interact. Our framework helps understand when ecological and evolutionary differences average out versus when their dynamical effects persist.

ecology↗

bioRxiv2026

Stressed alga-free coral cells can initiate coral bleaching

Coral bleaching is driving the rapid decline of coral reefs worldwide, yet a fundamental question remains unresolved: does the bleaching cascade begin in the coral host or in its intracellular algal symbionts, Symbiodiniaceae? Resolving where this process starts is critical for understanding how symbiosis collapses and where early intervention might be effective. Here we use transient stress to create a temporal window between the early cellular response and subsequent symbiosis breakdown. Across transient menthol and thermal stress in soft and stony corals, bleaching developed after the stress had ended. In Xenia sp., single-cell transcriptomics revealed a broad host response before detectable symbiont loss, including coordinated redox changes consistent with conditions favouring reactive oxygen species (ROS) accumulation. Cell-resolved imaging showed that alga-free coral cells were the first to become ROS-positive, whereas Symbiodiniaceae showed no detectable ROS signal. This early host response was transmissible. Conditioned medium from stressed cultures induced the emergence of ROS-positive host cells and subsequent symbiosis breakdown in unstressed recipients. Purified ROS-positive alga-free coral cells alone were sufficient to trigger symbiosis breakdown in recipient cultures without direct stress exposure. Suppressing the early emergence of ROS-positive coral cells markedly reduced later bleaching, whereas intervention after stress was substantially less effective. These findings identify a host-initiated, intercellularly propagating route to coral bleaching and reveal an early host response that can determine the subsequent fate of the symbiosis.

cell biology↗

bioRxiv2026

Ebola virus mRNAs contain RNA structures that are critical for viral infection and targetable by antisense oligonucleotides

Filoviruses, such as Ebola virus (EBOV), are highly pathogenic non-segmented negative-sense RNA viruses (nsNSVs) with limited therapeutic options. Filovirus RNA structures remain largely untapped due to the enhanced biosafety requirements for handling infectious virus. Here, we present the first in-cell secondary structure maps of four EBOV mRNAs (VP35, VP40, VP30, and VP24) using two orthogonal chemical probing approaches: SHAPE-MaP and fbDMS-MaP. We find that EBOV mRNA coding sequences (CDS) are highly structured, much like +ssRNA viruses, whereas untranslated regions (UTRs) are significantly less structured. This suggests that high CDS structure contents are general features of viral translation templates, and that nsNSVs have evolved separate regulatory function at the RNA structure level that extends beyond using distinct mRNAs and genomes. These structure maps are consistent with formation of mRNA 5' hairpin structures during infection and reveal numerous additional RNA structures within the CDS, 3' UTRs, and at CDS-UTR junctions. To assess functionality, we disrupted these structures with locked nucleic acid (LNA) antisense oligonucleotides. Disrupting the TSS hairpins in VP35, VP30, and VP24 decreased infection by >60%, indicating these mRNA structures are critical for infection. LNA targeting of the newly identified structures reduced EBOV infection by 31% to 88%, thereby linking RNA structural integrity to viral function. Synonymous mutation rates and covariation analysis provided evolutionary support across mammalian filoviruses for the functional RNA elements observed. Collectively, these results demonstrate EBOV mRNAs contain numerous conserved RNA motifs contributing to viral infection, and that these elements represent promising targets for development of pan-filoviral therapeutics.

microbiology↗

bioRxiv2026

PerturbTrace: Evaluating Feedback Use by AI Co-Scientist Agents in Perturbation Discovery

Recent advances in AI co-scientists have brought LLM agents into closed-loop experimental design. However, whether these agents use feedback from earlier rounds to revise subsequent experimental decisions remains unclear. We address this question with PerturbTrace, which evaluates each round-to-round transition through Feedback-to-State, State-to-Action, and Action-to-Outcome. These stages assess whether feedback is reflected in the agent's rationale and perturbation-selection strategy, whether the stated strategy guides the next perturbation batch, and whether that batch yields more hits than expected under random sampling. We evaluate four LLM agents on 17 screen-derived tasks and compare them with random selection, active learning, and LLM-guided Bayesian optimization baselines. Each agent outperforms the strongest non-agent method on at least 15 of the 17 tasks, yet controlled evaluations across six tasks show no consistent advantage from true feedback over random or no feedback. Among 576 transitions under true or random feedback, only 43 (7.5%) complete the full Feedback-State-Action-Outcome sequence, including 25 under random feedback. These findings show that high final recall does not necessarily indicate effective feedback use. They also highlight the need to evaluate closed-loop scientific agents by both their discovery performance and whether feedback changes their subsequent decisions.

bioinformatics↗

bioRxiv2026

Global transmission architecture of VIM carbapenemases reveals host-specific dissemination strategies

Carbapenemase-producing Gram-negative bacteria carrying Verona integron-encoded metallo-{beta}-lactamase (VIM) pose a persistent global threat, yet the mechanisms driving their worldwide dissemination remain poorly resolved. We analysed 5,617 blaVIM-positive genomes collected from 73 countries or regions across six continents between 1999 and 2025 to reconstruct the global epidemiology and transmission architecture of VIM carbapenemases. Forty VIM variants were identified across 16 bacterial genera, revealing marked host preferences and temporal shifts. VIM-2 dominated global circulation, whereas VIM-1 and VIM-4 remained prominent among Enterobacterales. Strikingly, VIM spread followed distinct host-specific evolutionary strategies. In Pseudomonas aeruginosa, dissemination was largely clone-driven, with high-risk lineages ST111 and ST235 supporting long-term persistence through lineage expansion and stable inheritance. By contrast, Enterobacterales were dominated by horizontal transmission through broad-host-range IncHI2A, IncA, and IncC plasmids, although only a limited subset of plasmid-VIM combinations achieved intercontinental spread. Among 2,828 loci with sufficient flanking sequence, 96.2% were embedded within integrative genetic elements, frequently nested with insertion sequences and phage-related elements, revealing a multilayered mobile-element network underlying VIM persistence. Structural analyses showed a highly conserved metallo-{beta}-lactamase scaffold but recurrent diversification near substrate-interacting residues, particularly positions 224 and 228. Shared genetic clusters between human-associated and environmental isolates further suggested cross-niche circulation. Together, these findings establish a hierarchical, host-dependent framework for global VIM dissemination, integrating clonal expansion, plasmid transfer, and nested mobile genetic elements. ImportanceBy analysing 5,617 blaVIM-positive genomes worldwide, this study reveals a host-dependent transmission architecture of VIM carbapenemases. In P. aeruginosa, VIM dissemination is mainly driven by expansion of successful high-risk clones, particularly ST111 and ST235, whereas in Enterobacterales it is primarily mediated by broad-host-range plasmids enabling cross-species transfer. Global VIM spread is not driven by a single dominant pathway but by a limited number of successful clone-plasmid-mobile element combinations, while most genetic backgrounds remain regionally restricted. These findings define a hierarchical transmission model of VIM evolution and provide insights for genomic surveillance and targeted control of metallo-{beta}-lactamase-mediated antimicrobial resistance.

microbiology↗

bioRxiv2026

GAMETE maps the genetic architecture of chromatin accessibility in rice pollen at single-nucleus resolution

BackgroundDissecting the genetic basis of cell-type-specific gene regulation during gametogenesis remains a major challenge. Population-level studies mask cellular heterogeneity, while the extreme data sparsity of single-cell profiling has precluded robust genetic mapping. ResultsWe present GAMETE (Genetic Architecture Mapping of Epigenetic Traits at single-nucleus resolution), an integrated framework combining MPS-ATAC-seq, a high-throughput single-nucleus ATAC-seq method, with robust computational approaches for genotype inference and genetic mapping from sparse single-nucleus data. Applying GAMETE to hybrid rice pollen, we simultaneously profiled chromatin accessibility and inferred the genotypes of 4,887 individual haploid nuclei, revealing distinct chromatin landscapes across pollen cell types. This uncovered an unexpected elevation of chromatin accessibility at gypsy retrotransposons in microspores preceding their silencing in sperm cells, exposing a surveillance gap that may contribute to genome expansion. The synchronized profiling enabled us to construct a single-cell recombination map, map segregation distortion loci and trace their developmental origins, and identify 16,113 chromatin accessibility QTLs (caQTLs), 48.6% of which exhibited pronounced cell-type specificity. Analysis of introgression lines supported a cell-type-specific trans-acting caQTL regulating the pollen-essential gene DTM1. ConclusionsThis work establishes GAMETE as a broadly applicable framework for dissecting the genetic architecture of chromatin accessibility during gametogenesis without the need for subsequent generations.

genomics↗

bioRxiv2026

A Divergent Class of Arylamine N-Acetyltransferases Catalyzes Convergent Amidative Condensation of Polyketides in Manumycins Biosynthesis

Polyketides are prized for their structural complexity and therapeutic potential, yet the incorporation of amide bonds into their frameworks typically relies on linear, nonribosomal peptide synthetase (NRPS)-dependent assembly. The direct, convergent coupling of distinct polyketide chains via amide bond formation--an ideal strategy for combinatorial biosynthesis--has remained largely elusive. Here, we report the discovery of a novel family of arylamine N-acetyltransferases (NATs) from manumycin-type biosynthetic pathways that catalyze an unprecedented intermolecular amidative chain transfer/condensation between an acyl carrier protein (ACP)-tethered polyketide donor and a free polyketide acceptor. Biochemical, structural, and molecular dynamics studies reveal that the representative enzyme, ColC2, possesses a distinctive substrate-binding pocket that diverges from canonical arylamine NATs, conferring exceptional promiscuity toward diverse acyl donors and acceptors. We demonstrate the utility of this biocatalyst by coupling arylamines with either synthetic acyl-thioesters or polyketide synthase (PKS) machinery to generate a library of non-natural polyketide amides and manumycin derivatives. These findings establish a new paradigm for amide bond formation in polyketide biosynthesis and position arylamine NATs as powerful tools for the development of novel therapeutics through combinatorial synthesis.

synthetic biology↗

bioRxiv2026

Leptin Receptor+ cells create a perisinusoidal niche for thrombopoiesis in the bone marrow by synthesizing CXCL14

Leptin Receptor-expressing (LepR+) stromal cells in the bone marrow are a critical source of growth factors for the maintenance of hematopoietic stem cells (HSCs) and most restricted hematopoietic progenitors. An important unresolved question is whether they also regulate terminal differentiation in some hematopoietic cells. We found that LepR+ cells promote thrombopoiesis by synthesizing the chemokine CXCL14, which is expressed in the bone marrow by a subset of LepR+ cells. Cxcl14-expressing LepR+ cells extend fine processes that wrap around perisinusoidal megakaryocytes. Deletion of Cxcl14 from LepR+ cells did not significantly alter HSC function or most aspects of bone marrow hematopoiesis, including megakaryocyte generation; however, it significantly reduced the numbers of proplatelet-forming megakaryocytes in the bone marrow and platelets in the blood. CXCL14 promoted platelet formation by remodeling lipid metabolism in megakaryocytes, increasing fatty acid transporter expression and enabling megakaryocytes to take up more polyunsaturated fatty acids from circulation. A high fat diet rescued the formation of proplatelet-forming megakaryocytes and platelets in Lepr-cre; Cxcl14 fl/fl mice. CXCL14 protein was sufficient to promote platelet formation by megakaryocytes in vitro and in vivo. LepR+ cells thus create a perisinusoidal niche for thrombopoiesis by producing CXCL14, which regulates lipid metabolism and terminal differentiation in megakaryocytes. Key pointsO_LILeptin Receptor+ stromal cells regulate terminal differentiation in megakaryocytes in addition to maintaining stem and progenitor cells C_LIO_LICXCL14 from Leptin Receptor+ cells promotes the formation of platelets by remodeling lipid metabolism in megakaryocytes in the bone marrow C_LI

cell biology↗

bioRxiv2026

A comprehensive analysis of flagellar mutations in Vibrio cholerae: Trade-off mechanisms between motility loss and host adaptability

IntroductionCholera, caused by Vibrio cholerae, is a severe diarrheal disease threatening global health. The flagellum of V. cholerae functions not only for motility but also as an environmental sensor regulating virulence. The trade-off mechanism between motility loss and enhanced host adaptation remains unclear. ObjectiveThis study aimed to elucidate how flagellar mutations, which lead to a loss of motility, affect host adaptability in V. cholerae and to uncover the underlying molecular basis. MethodsWe analyzed 3,135 cholera-related samples to identify mutation hotspots in flagellar genes. A relevant flagellar mutant library was constructed and assessed for host adaptability. Multiple approaches, including molecular, genetic, transcriptomic, and proteomic analyses, were applied to dissect the FlgM-mediated pathway, with key findings revalidated in an adult mouse model using a specifically constructed 6N-labeled mutant pool. ResultsBig data analysis reveals those flagellar mutations in V. cholerae cluster in key structural and regulatory genes, including flhB, fliA, fliF, fliD, and fliM. Flagellar mutations led to a scenario where the secretion level of the regulator FlgM was negatively correlated with host adaptability. Intracellular FlgM inactivates either the {sigma}28 factor FliA directly or acts through the VarS/VarA-CsrA/BCD system, ultimately leading to the derepression of the quorum-sensing master regulator named hapR. HapR can directly bind to the promoters of genes involving in methionine transportation to regulate adaptability of V. cholerae. The 6N-labeled mutants pool experiment reconfirmed that motility loss promotes host adaptability via the FlgM-FliA-HapR-methionine axis. ConclusionOur findings demonstrate that secretion levels of the flagellar regulator FlgM drive an adaptive shift in V. cholerae from motility to host adaptability, mediated through quorum sensing and methionine metabolic reprogramming. This reveals a novel mechanism underlying bacterial evolution and pathogenicity.

microbiology↗

bioRxiv2025

Trichome formation in Nicotiana benthamiana is induced by Agrobacterium

Plant trichomes are specialised epidermal appendages found on various organs of many plant species. They play important roles in plant protection against pests, pathogens, herbivores, resistance to abiotic stress, light perception, mechanosensitivity etc. They are of direct agricultural importance, providing fibre (e.g. cotton) and producing secondary metabolites essential for agriculture, medicine, and industry. Trichomes can be relatively sparsely distributed, making their biological investigation and commercial exploitation more challenging. Here we show that infiltration of Nicotiana benthamiana leaf tissue with certain nopaline-type Agrobacterium tumefacians strains induces extremely dense, localised formation of glandular trichomes 15 days post infiltration (dpi). This Agrobacterium-strain specific effect was shown to be due to the presence of a trans-zeatin synthase (tzs) gene located on some Ti plasmids, which results in the bacterial production of the cytokinin trans-zeatin. This simple procedure enables dramatically increased trichome density to be compared biologically with adjacent isogenic plant tissues on the same leaf.

plant biology↗

bioRxiv2025

Fire removes preexisting pyrogenic organic matter from the ecosystem through the mechanisms of both direct combustion and increasing mineralizability

Pyrogenic organic matter (PyOM) produced during fires plays an important role in the global carbon (C) cycle due to its low microbial availability and resulting high persistence. However, PyOM can be combusted or chemically altered in subsequent fires. To explore the effect of subsequent fire on PyOM, we used a mass loss calorimeter to deliver realistic heat fluxes to jack pine (Pinus banksiana Lamb.) PyOM produced at 350 {degrees}C, testing heat flux profiles (High, Low, and Control) and burial depths (Surface, 1 cm, and 5 cm) in a full-factorial design. We found that both variables significantly affected the C remaining after burns (p < 0.05), with greater C losses at higher heat fluxes and shallower exposure depths. Consistent with our predictions, treatments with high heat exposure (HFHigh+Surface, HFHigh+1cm, HFLow+Surface) showed increases in pH and decreases in total dissolved organic carbon (DOC) and mineralized C after the subsequent fire. Counter to our predictions, treatments with intermediate heat exposure (HFHigh+5cm and HFLow+1cm) caused significant decreases in pH and increases in DOC, mineralized C, modelled decomposable C, and modelled C decomposition rate (p < 0.05), compared to the unburned controls. These findings highlight that, despite its high persistence in fire-free conditions, PyOM is readily combusted and altered in subsequent fires, with important implications for changing fire regimes and the global C cycle. Synopsis StatementSubsequent fires not only consume PyOM produced in previous burns, but can also increase its susceptibility to microbial decomposition, which challenges the potential for PyOM to contribute to long-term carbon storage.

ecology↗

bioRxiv2025

Analysis of SIV Spatiotemporal Dissemination Patterns in Rhesus Macaques During Early Rectal Transmission Demonstrates Systemic Infection Does Not Require Viral Local Amplification at the Entry Portal

Receptive anal sex is a dominant mode of HIV-1 (HIV) transmission, especially among men who have sex with men (MSM). However, the early events during HIV rectal transmission are not well understood and many questions remain, such as, does virus local amplification at the entry portal require for viral distal seeding? What is the spatiotemporal dissemination pattern across whole body? How do three viral forms, i.e., cell-free virus (VCF), cell-associated virus (VCA), and follicular dendritic cell-trapped virus (VFDC), evolve during early infections? To close this knowledge gap, we comprehensively examined rectum, draining lymph nodes (dLN) and distal lymph nodes (disLN), as well as non-lymphoid organs of brain, lungs, and liver of Indian rhesus macaques (RMs) at the early time points following intrarectal SIVmac251 inoculation (1, 2, 3, 4, 6, 10 14, 28 day post inoculation, dpi). Our findings demonstrated SIV rapidly disseminates to distant tissues and organs (<=1 dpi) and virus local amplification in rectum and dLN is not required for viral distal seeding for the establishment of systemic infection, viral forms shift from VCF and VCA to VFDC accompanying from T cell zones into B cell follicles. Collectively, these findings indicate that an effective HIV vaccine needs to induce immune protection both locally at sites of viral entry and systemically.

immunology↗

bioRxiv2025

The dominance of gene expression controlled by trans-eQTL hotspots contributes to phenotypic heterosis in maize

Heterosis, or hybrid vigor, is a key phenomenon in genetics research and agricultural production, and has been primarily attributed to non-additive genetic effects such as dominance -- a prevailing consensus shaped by decades of empirical research and theoretical debate. Although dominance may arguably arise from distal modifiers, their selective advantage is debated due to presumably small individual effects. To address this long-standing question, particularly how genetic dominance manifests at the transcriptomic level and contributes to phenotypic heterosis, we integrated transcriptomic and phenotypic data from a large population of maize hybrids and their inbred parents. We found that [~] 30% of the expressed seedling genes in a significant proportion of hybrids exhibited expression patterns deviating from the average of the two parents, indicative of non-additivity. Further analysis suggests that while hybrid gene expression per se is primarily regulated by cis-eQTLs, expression dominance (or non-additivity) is disproportionately controlled by trans-eQTLs. These trans-eQTLs cluster into hotspots that regulate the non-additivity of hundreds of target genes, mostly within co-expression networks, and are notably enriched for transcription factors (TFs). Focusing on one such hotspot, we functionally validated a classical maize gene ZmR1, a basic helix-loop-helix (bHLH) TF associated with multiple seedling trait heterosis, as a candidate regulator of expression dominance across hundreds of genes. Overexpression of ZmR1 enhances expression dominance of downstream genes and increases phenotypic heterosis in both seedling and adult traits. Further experiments confirmed its direct regulatory role in modulating genes involved in anthocyanin biosynthesis and lignin metabolism, driving transcriptome-level dominance. These results provide empirical support for the modifier hypothesis under an omnigenic model, suggesting that heterosis arises not from the modification of a single genes inheritance but through the coordinated regulation of hundreds of phenotype-associated genes, thereby helping to reconcile the long-standing debate over the genetic basis of dominance in heterosis.

genetics↗

bioRxiv2025

A spatially-resolved human brain proteome atlas for understanding function and disease

While the brain performs specialized functions across distinct regions, the spatial organization of the human brain proteome remains largely uncharted. Here we present a comprehensive spatially-resolved proteome atlas of the human brain, analyzing over two thousand MRI- guided locations across four individuals. Proteome analysis integrated with transcriptomics reveals extensive post-transcriptional regulation, with cortical regions showing markedly higher protein diversity than transcript. Unsupervised molecular clustering defines distinct brain territories that transcend anatomical boundaries, instead reflecting metabolic demands and functional specialization patterns. Application to epilepsy brain tissue uncovered disrupted astrocyte metabolism, protein homeostasis and therapeutic targets including the seizure-associated purinergic receptor P2RX7. This resource bridges molecular and systems neuroscience to accelerate neurological drug discovery.

neuroscience↗

bioRxiv2025

Climate-Driven Ecosystem Productivity Changes Restructure Food Systems

Climate change affects food systems through multiple pathways, yet the isolated effects of climate-driven ecosystem productivity changes remain poorly understood. While field studies translate productivity changes to crop yields, at larger scales yield conflates productivity with management and technology, and critically, productivity changes occur across all vegetation types, not just agricultural lands. We isolate ecosystem productivity changes to trace their propagation through food systems across three socioeconomic scenarios (SSP1-2.6, SSP3-7.0, SSP5-8.5) by coupling the CLASSIC land surface model with GCAM integrated assessment model. Productivity changes lead to crops systematically shifting from human consumption to animal feed and bioenergy (up to 15% reallocation), while there is a significant transition of managed agricultural lands to unmanaged lands by up to 6 million km2 as productivity gains enable less intensive land use. These changes drive extreme regional divergence, with food production volume changing from +35% to -28% and substantial portfolio reorganization. Disruptions peak under regional rivalry (SSP3-7.0), revealing how fragmented governance amplifies biophysical feedbacks beyond climate forcing alone. While how much we eat may remain stable, ecosystem productivity fundamentally reshapes what we eat and where to source it.

ecology↗

bioRxiv2025

Water body size shapes body size evolution via subgenomic selection in allopolyploid fish

Allopolyploidization is a major force in species evolution, and studying allopolyploids in diverse environments provides insights into their genetic mechanisms. Here, we investigated how water body size variation influences body size in allopolyploid fish. We used a nascent allopolyploid lineage derived from goldfish (Carassius auratus) and common carp (Cyprinus carpio) and established two populations in small and large water bodies for two generations. Genomic, transcriptomic, and epigenomic analyses revealed that the larger population had higher genetic diversity in subgenome R, while the smaller population had higher diversity in subgenome C. Potential selection regions were associated with growth regulatory genes, suggesting a role for gene regulation in body size adaptation. Dynamic gene expression patterns in various tissues indicated potential mechanisms underlying muscle development and adaptation to smaller water bodies. Furthermore, selection regions were linked to changes in chromatin accessibility, with subgenome R being more susceptible to these changes during genetic divergence. Our findings demonstrate that water body size variation drives body size in allopolyploid fish through subgenomic selection, impacting genetic variation, gene regulation, and epigenetic mechanisms.

genomics↗

bioRxiv2025

SARS-CoV-2 NSP14 inhibitor exhibits potent antiviral activity and reverses NSP14-driven host modulation

The emergence of SARS-CoV-2 variants and drug-resistant mutants highlights the urgent need for novel antiviral therapeutics. SARS-CoV-2 NSP14, an N7-guanosine methyltransferase, plays a critical role in viral RNA capping, enabling viral replication and immune evasion. While NSP14 has emerged as a promising drug target, its role in host-virus crosstalk and the cellular consequences of NSP14 inhibition remain poorly understood. Here, we present the identification and characterization of C10, a highly potent and selective first-in-class non-nucleoside inhibitor of the NSP14 S-adenosylmethionine (SAM)-binding pocket. C10 demonstrates robust antiviral activity against SARS-CoV-2, including its variants, with EC50 values ranging from 64.03 to 301.9 nM, comparable to the FDA-approved drug remdesivir in our cell-based assays. C10 also exhibits broad-spectrum activity against other betacoronaviruses and inhibits SARS-CoV-2 at the replication stage. C10 suppresses viral translation and exhibits immunostimulatory effect. Additionally, C10 specifically reversed NSP14-mediated alterations in host transcriptome. The antiviral efficacy of C10 was further validated in a transgenic mouse model of SARS-CoV-2 infection. Our findings highlight C10 as a promising candidate for the development of effective treatments against SARS-CoV-2 and its emerging variants. This study also uncovers a novel mechanism of NSP14 in SARS-CoV-2 pathogenesis and its therapeutic potential, providing insights that may extend to other viral capping methyltransferases.

microbiology↗

bioRxiv2025

DAXX governs the silencing of LINE1 during spermatogenesis in mice

The suppression of transposable elements in germline is critical for safeguarding fertility. Here we identify that the DAXX, a potent transcription repressor and an H3.3 chaperone, is indispensable for transposable elements silencing during spermatogenesis. Male mice with conditional knockout of Daxx in germ cells mediated by Ddx4-cre display delayed meiotic progression, deformed and reduced production of sperms, and an age-dependent decline in fertility. The ablation of DAXX results in activation of evolutionarily young LINE1 and ERVs subfamilies. Mechanistically, DAXX interacts with DMAP1 to maintain DNA methylation of LINE1 in meiotic cells. In summary, this study identifies DAXX as a previously unknown regulator of spermatogenesis and demonstrates that it functions as an epigenetic regulator to maintain the silencing the young LINE1 by DNA methylation.

developmental biology↗