Biology subjects

Wang, D.

Publications and source records attributed to Wang, D..

At least 19 recordsLinked to original sources

bioRxiv2026

DNA sequence sets the destination of spontaneous epimutations in plants

Plant genomes gain and lose cytosine methylation spontaneously, far faster than DNA mutates, and these epimutations are inherited. The genome is thought to set a steady state around which methylation fluctuates. Here we show that this steady state, the set point, is written in the DNA of each CG site: REED, a deep-learning model trained on one methylome, reads it. In pedigrees of seven Arabidopsis thaliana accessions, gains concentrated at high set points and losses at low ones, and the equilibrium implied by their rates matched the set point, tracking it within genes. Stress sped epimutation but barely shifted its destination. The set point predicted germline epimutations in rice and changes accumulated in the wild and in a 330-year-old tree. Its rules, cooperation between nearby CG sites and transcription-factor motifs that lower methylation, are shared across flowering plants, so a genome and one methylome reveal where epigenetic variation is heading.

plant biology↗

bioRxiv2026

Glymphatic System Is Enhanced in Anti-NMDAR Encephalitis and Facilitates Antibody Influx and Clearance in the Brain

ABSTRACT Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an antibody-mediated neuroinflammatory disease. How pathogenic autoantibodies enter and are cleared from the brain parenchyma remains poorly understood. The glymphatic system (GS) mediates cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange and waste removal, yet its role in anti-NMDAR encephalitis is undefined. Methods: We used polypeptides GluN1356-385 induced active-immunization anti-NMDAR encephalitis mouse model. Glymphatic influx and efflux were evaluated via fluorescent tracer delivery combined with real-time imaging and ex-vivo quantification. Perivascular aquaporin-4 (AQP4) polarization, brain IgG deposition, NMDAR levels and blood-brain barrier (BBB) integrity were analyzed. GS function was pharmacologically modulated with AER-271 (an AQP4 inhibitor) or dexmedetomidine (Dex), and deep cervical lymphatic vessels (dCLV) were ligated in a passive-transfer model (PTM). Behavioral performance was characterized by multiple neurobehavioral tests. Results: Both glymphatic influx and efflux were enhanced in anti-NMDAR encephalitis mice, accompanied by upregulated antibody entry into and clearance from the brain. However, the cerebral IgG deposition was increased. These changes were associated with increased perivascular AQP4 polarization, with no alterations in overall AQP4 abundance or BBB tight-junction integrity. AQP4 inhibition with AER-271 attenuated glymphatic influx and efflux, reduced hippocampus IgG deposition, and partially ameliorated behavioral deficits without restoring hippocampus NMDAR levels. Conversely, dCLV ligation in the PTM mice increased brain retention of patient-derived IgG and exacerbated anxiety-like behavior. Dex enhanced antibody clearance and reduced hippocampus IgG deposition but did not improve behavioral outcomes. Conclusion: The GS is dynamically upregulated in anti-NMDAR encephalitis, driven by increased perivascular AQP4 polarization. The enhanced glymphatic influx facilitates antibody entry into the brain parenchyma and exacerbates neuronal injury, whereas enhanced efflux provides a compensatory route for antibody clearance. Rather than broadly enhancing glymphatic activity, precise tuning of this pathway may present a promising non-immunological therapeutic strategy for autoimmune encephalitis. Keywords: anti-NMDAR encephalitis; antibody influx and clearance; glymphatic system; AQP4 polarization; AER-271; dexmedetomidine

neuroscience↗

bioRxiv2026

LysM: a bacterial self-encoded peptidoglycan hydrolase as an antimicrobial and anti-biofilm agent for Gram-negative nosocomial pathogens

Agents with both anti-biofilm property and broad-spectrum antimicrobial activity are urgently needed, especially for drug-resistant nosocomial pathogens. Here, we report a bacterial genome-encoded glycoside hydrolase, named LysM, with lytic activity against multiple Gram-negative nosocomial pathogens and little toxicity to human cells. 3D structural modelling and site-directed mutagenesis indicates that LysM is a peptidoglycan-specific glycoside hydrolase. In combination with EDTA, exogenous LysM induces explosive bacterial cell lysis, exhibits potent bactericidal activity, and eliminates 24 h-old biofilms formed by Gram-negative ESKAPE group pathogens with the highest activity on three nosocomial pathogens, namely Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacter cloacae, all of which contain LysM homologs in their genome. More strikingly, LysM supplied in growth media without EDTA, also inhibits the growth of several nosocomial pathogens. Single-cell tracking analysis reveals that LysM completely prevent biofilm formation of P. aeruginosa by reducing bacterial surface-adherence and extending the doubling time. A LysM-based cocktail consisting of LysM, EDTA, and matrix exopolysaccharide-degrading glycosidase PslG, shows potent anti-biofilm activity against P. aeruginosa, including drug-resistant clinical isolates, both in vitro and in human airway organoids (HAOs) biofilm infection model. In addition, LysM enhances the efficacy of many antibiotics from all major classes, including colistin, tobramycin, ciprofloxacin, and tetracycline. Our findings not only provide a clinical candidate for the treatment of nosocomial infections but also open a new path for antimicrobial discovery and anti-biofilm strategies, as homologues of LysM are present in the genomes of many bacteria and phages.

microbiology↗

bioRxiv2026

Programmable Surface Receptor-Mediated Cell Targeting with Designer Antibody-Routed Nanoparticles (DARTs)

Precise in vivo delivery remains a massive barrier to therapeutic genome editing. Recently, major strides have been made towards cell type-specific delivery, with potential to improve the safety profiles of future gene therapies. However, programming such targeted tropism is limited by the minimal repertoire of scFv sequences, nanobodies, and viral fusogens that enable cell-type specificity, and the slow, iterative design-build-test cycle required to identify and optimize them. Here, we overcome this bottleneck by developing the designer antibody-routed (DART) platform: a modular, plug-and-play tool that decouples delivery vehicle production from tropism engineering. By presenting generic, bioorthogonal antibody-binding interfaces on the surfaces of enveloped particles, the DART system enables conjugation of those particles with off-the-shelf antibodies that direct cell entry without requiring genetic or chemical manipulation. Designer antibody-routed virus-like particles (DARTs) leverage this facile conjugation method to interrogate and identify transduction-competent surface antigens across cell types. They enable combinatorial targeting and the discovery of antigens that synergistically enhance transduction. Finally, DARTs function in the fetal murine nervous system, empirically identifying CD56 as a previously uncharacterized surface antigen enabling editing in hard-to-transduce neural populations. Overall, the DART platform provides a universal tool for rapidly profiling unique, targetable antigens and leveraging them for precision editing applications.

bioengineering↗

bioRxiv2026

DCAF: Unifying Data Validity, Evaluation Validity and Predictive Modeling for Single-cell Perturbation Simulation

Single-cell perturbation profiling is limited by cost and throughput, while computational methods remain constrained by inconsistent evaluation and underperformance relative to simple baselines. Here we present DCAF, a unified framework for single-cell perturbation simulation that that jointly addresses data validity, evaluation validity and predictive modeling. Among its three components, DCAF-data addresses the single-measurement limitation by reconstructing pre- and post-perturbation status using entropy-regularized optimal transport, and is demonstrated on both cell line and multi-cell type datasets. DCAF-criterion evaluates log fold changes in non-silenced genes to improve sensitivity to model error and robustness to zero inflation noise, validated on synthetic datasets. DCAF-model combines JEPA with explicit modeling for regulatory-dynamics modeling for interpretable prediction. Across benchmarks, DCAF outperforms state-of-the-art deep-learning methods, as well as mean and linear baselines in cross-gene, cross-cell-type and cross-region generalization. In adult Mouse brain, DCAF recapitulates known cell-type-specific regulatory heterogeneity of Dgcr8 knockdown at both cell type and gene levels. DCAF thus provides a rigorous and biologically grounded foundation for reliable perturbation simulation across development, disease and therapeutic discovery.

bioinformatics↗

bioRxiv2026

Spatially resolved host-fungal transcriptomics profiling by fungal-DBiT

Hosts and their associated fungi coexist within a shared tissue environment, engaging in dynamic interactions that influence immune regulation, tissue homeostasis, and disease progression. Dissecting these interactions requires spatially resolved and unbiased approaches capable of capturing gene expression from both host and fungal cells within intact tissue architecture. Here, we present fungal-DBiT, a spatial transcriptomic platform that enables simultaneous, high-resolution mapping of host and fungal RNAs, directly in tissue sections. Using fungal-DBiT, we profiled the spatial distribution of host and fungal transcripts in a fungal infection mouse model, and review pronounced spatial heterogeneity in fungal localization and activity, accompanied by region-specific host transcriptional responses. We further applied fungal-DBiT to intestinal tissues under physiological conditions, demonstrating its sensitivity in detecting low-abundance fungal species in the absence of overt inflammation. Together, these results demonstrate the ability of fungal-DBiT to resolve host-fungal interactions in situ and highlight its utility for studying mycobiome associated immune responses and disease processes with spatial precision.

microbiology↗

bioRxiv2026

Valine Engages a Prefrontal mGluR5 Allosteric Site to Preserve Social Behavior

Branched-chain amino acid metabolism is linked to neurodevelopmental disorders, but whether a defined amino acid directly modulates cortical receptor signaling to control behavior is unknown. Here, we show that valine is uniquely required for sociability through medial prefrontal cortex (mPFC) circuitry. Partial dietary valine restriction, but not comparable leucine or isoleucine restriction, or mPFC-restricted acceleration of BCAA catabolism through Bckdk loss, disrupts social interaction, and local valine supplementation rescues behavior. LiP-SMap, surface plasmon resonance, cryo-EM, and mutagenesis identify metabotropic glutamate receptor 5 (mGluR5) as a direct valine target and reveal a valine-selective allosteric pocket distinct from the glutamate site. Valine is signaling-biased: it drives {beta}-arrestin-linked output yet has little standalone Gq efficacy, instead potentiating glutamate-evoked mGluR5 signaling to recruit endocannabinoid/CB1 feedback, gate inhibitory transmission, and preserve mPFC-dependent social behavior. Together, these findings identify valine as a diet-derived allosteric ligand that links amino acid availability to cortical circuit control of social behavior.

neuroscience↗

bioRxiv2026

Charting sex divergence in the human brain across the lifespan

Biological sex fundamentally shapes human brain organization, but sex-specific normative neuroanatomical trajectories across the lifespan remain largely uncharted. Here, we constructed independent, sex-specific lifespan brain charts using structural neuroimaging data from 59,915 healthy individuals (29,760 males and 30,155 females) ranging in age from 266 postconception days to 100 years. By examining 296 structural phenotypes across global, cortical, and subcortical measures, these models revealed widespread sex differences in maturational timing, with males reaching peak milestones later than females. These trajectories demonstrate that sex differences evolve dynamically, with phenotype-specific windows of emergence and maximal separation. Compared with conventional sex-pooled references, sex-specific models achieved superior predictive accuracy and reduced misestimation of individual deviations in healthy populations. Across five neuropsychiatric conditions, sex-specific models improved the detection of extreme deviations and revealed both shared and sex-dependent patterns of disorder-related neuroanatomical abnormalities. These sex-specific charts establish tailored normative references for assessing brain development, ageing, and disease.

neuroscience↗

bioRxiv2026

Multi-omics reveals accumulation mechanisms underlying differences in sesquiterpenoid content across different growth environments of Atractylodes macrocephala rhizome

This study aimed to explore mechanisms driving differential sesquiterpenoid accumulation in Atractylodes macrocephala rhizome (AMR) under different growth environments. Root and rhizosphere soil samples were collected from wild, imitated wild, one- and two-year cultivated AMR. Combined metabolomic, transcriptomic and microbiomic profiling was carried out to investigate alterations in sesquiterpenoid levels, root-associated microbiota, and terpenoid biosynthetic genes under different growth environments. Metabolomics revealed that wild AMR exhibited higher pyruvate consumption and accumulated more atractylone and atractylenolides. Transcriptomic analysis demonstrated that the genes encoding key MEP pathway enzymes (DXS, DXR, MCT, HDS) and the genes encoding the sesquiterpenoid biosynthetic enzyme GDS were significantly upregulated in wild AMR. In contrast, the genes encoding triterpenoid synthetic enzymes (SQS, SQE, {beta}-AS) were downregulated, redirecting metabolic precursors toward sesquiterpenoid synthesis. Microbial community structures differed substantially across groups. Further analysis suggested rhizosphere microorganisms were important contributors to AMR medicinal quality, and sesquiterpenoid metabolites accumulated in AMR roots, together with the rhizosphere microenvironment, jointly shape specific rhizosphere fungal assembly. This study systematically revealed the synergistic regulatory relationships among sesquiterpenoids metabolism, gene expression, growth environment, and root-associated microbes, providing multi-omics evidence for clarifying the mechanism by which these factors coordinately regulate the quality of AMR.

plant biology↗

bioRxiv2026

The cleaved C-terminal domain of GmERS1-1 modulates cell cycle via GmACR1

Ethylene signaling orchestrates plant development and stress adaptation, yet how post-translational modifications of its receptors coordinate growth regulation remains unresolved. Here, we uncover a proteolytic processing mechanism of the soybean ethylene receptor GmERS1-1 that directly gates cell cycle progression. The GmERS1-1 mutants exhibit elevated yield under field conditions, whereas overexpression suppresses growth and hypersensitizes plants to ethylene. Ethylene triggers nuclear translocation of C-terminal domain (GmERS1-1-CEND), which is indispensable for receptor function. Mechanistically, GmERS1-1-CEND scaffolds a trimeric complex with GmACR1 and GmCDK7, enforcing G2/M phase arrest, thereby decoupling cell division from canonical ethylene transcriptional responses. Strikingly, ethylene-induced cell cycle blockade during apple fruit maturation mirrors this pathway, suggesting deep conservation across angiosperms. Our work defines a receptor processing-dependent signaling axis that directly interlinks phytohormone perception with cell cycle control, proposing tunable targets (e.g., GmERS1-1 cleavage efficiency) for engineering crop architecture and productivity.

plant biology↗

bioRxiv2026

Desmoglein-1 coordinates cell proliferation and actin dynamics to promote epidermal morphogenesis.

Skin development depends on coordinated biochemical and mechanical signaling to form a multilayered epidermal barrier. Our previous work demonstrated that the stratified tissue-specific desmosomal cadherin Desmoglein-1 (Dsg1) promotes epidermal differentiation in human in vitro models. Dsg1 first appears in the developing mouse epidermis around E14, coinciding with a developmental transition in stratification and the onset of terminal differentiation, raising the question of how Dsg1 contributes to epidermal morphogenesis in vivo. We generated a wild-type (WT) single-cell RNA sequencing (scRNA-seq) atlas of murine skin and integrated scRNA-seq data from Dsg1 knockout (Dsg1 KO) embryos spanning E14.5, E15.5, E16.5, and E18.5. Six keratinocyte subpopulations were annotated, including a Transitional subpopulation co-expressing basal and suprabasal markers, positioned between basal and differentiated states. Dsg1 KO epidermis exhibited reduced thickness at E14.5-E15.5, but recovered by E16.5-E18.5, suggesting compensatory adaptation. Differential gene expression analysis revealed enrichment of cell-cycle and actin-associated programs in Dsg1 KO during late development. EdU incorporation and PCNA staining confirmed increased proliferation in superficial layers accompanied by altered actin organization and changed cell morphology. Notably, actin and the Arp2/3 actin nucleation-promoting factor N-WASP exhibited marked changes in distribution during early and late development, respectively. Mechanistically, Dsg1 associates with Nck1, an adaptor linking N-WASP to Arp2/3-dependent actin polymerization. Silencing Nck1 or N-WASP reduced Dsg1-mediated stratification significantly, while a Nck1-binding-deficient Dsg1 mutant failed to rescue stratification in Dsg1-deficient keratinocytes in vitro. Together, these findings identify a Dsg1-Nck1-N-WASP axis linking desmosomal adhesion to cytoskeletal remodeling and support a model in which Dsg1 coordinates cell-cycle, cell morphology, and actin dynamics to drive epidermal morphogenesis.

cell biology↗

bioRxiv2026

De novo design of functional RNAs through higher-order interactions

Designing RNA sequences that reliably adopt functional three-dimensional structures remains a central challenge in RNA engineering because folding depends on cooperative interactions beyond canonical base pairing. Here we present DS3dRNA, an interaction-based framework for de novo RNA sequence design that combines a three-body statistical potential with physics-guided sequence sampling and supports design against multiple conformations. Across the evaluated benchmarks, DS3dRNA outperformed representative RNA inverse-design methods in native-sequence recovery and agreement between predicted and target structures. Energy-sequence-quality analyses further showed that lower design energies generally accompanied higher sequence recovery and macro-averaged F1 scores (MacroF1). Experimentally tested Mango II designs retained high-affinity fluorogenic activity, and five twister ribozyme designs yielded mean endpoint cleavage fractions of 37.7-50.6%, compared with 23.5% for the wild type. These results establish explicit higher-order interaction scoring as a complementary approach to emerging data-driven RNA design methods and provide a framework for designing functional RNAs from experimental or predicted structural ensembles.

biophysics↗

bioRxiv2026

CycDelta: Multimodal Residue-Graph Learning of Permeability Changes in Cyclic Peptides

Membrane permeability remains a major challenge in cyclic-peptide drug discovery, where optimization often depends on estimating changes relative to measured reference compounds. Existing predictors mainly model absolute permeability, while heterogeneity across literature sources complicates pooled training and comparative evaluation. We present CycDelta, a multimodal residue-graph model trained directly on within-source permeability differences. CycDelta combines directed message passing with pretrained Uni-Mol monomer embeddings, physicochemical descriptors and assay information in a shared encoder for reference and query peptides. To evaluate this comparative formulation under controlled conditions, we establish CycDeltaBench, comprising in-distribution, scaffold-based out-of-distribution, external and zero-shot unseen-assay tests. On the out-of-distribution task, CycDelta achieved Pearson 0.69 versus 0.46 for the strongest baseline. It also led all evaluated methods on two external data sets and achieved zero-shot Spearman 0.70 versus 0.32 for the strongest baseline on an unseen assay. Residue-level attribution relates predictions to monomer contributions, while gradient-guided screening supports prioritization of permeability-enhancing analogue hypotheses. These results position CycDelta as a transferable and interpretable framework for comparative permeability prediction and cyclic-peptide optimization.

bioinformatics↗

bioRxiv2026

Rapid classification of β-lactamase activity through AI-based structure prediction and electric field analysis

Antibiotic resistance driven by {beta}-lactamases has become a major threat to public health. Here, we propose a computational protocol for rapid estimation of {beta}-lactamase activity towards carbapenem antibiotics from sequence alone. Starting from AI-predicted acylenzyme complexes, only approximate transition state ensembles are sampled to compute catalytic electric fields, which strongly correlate with experimental activation barriers (R2 = 0.8). Compared with full quantum mechanics/molecular mechanics (QM/MM) reaction simulations, the protocol substantially reduces the amount of configurational sampling and thus computational cost. Our protocol enables efficient identification of carbapenem breakdown efficiency, further highlighting the important role of electric fields in enzyme catalysis.

biochemistry↗

bioRxiv2026

A general method to develop excitation ratiometric neuropeptide sensors with enhanced sensitivity for in vivo applications

Neuropeptides regulate a wide range of physiological processes throughout the nervous and endocrine systems, yet their spatiotemporal dynamics in vivo remain poorly understood. While recently developed intensiometric sensors can detect neuropeptides, their use in vivo is often confounded by artifacts induced by hemodynamic changes, pH fluctuations, and motion. Here, we present a general strategy for engineering dual-excitation ratiometric (Ex-ratiometric) neuropeptide sensors by tuning the excited-state proton transfer properties of the fluorescent reporter. Dual excitation at 405 nm and 488 nm produces a ratiometric signal that intrinsically corrects fluorescence fluctuations unrelated to ligand binding. Using an AlphaFold3-guided in silico design approach combined with experimental validation, we developed a suite of Ex-ratiometric sensors. As a representative example, Ex-NTS2.0 enables robust detection of neurotensin (NTS) in vivo while remaining largely resistant to hemodynamics, pH, and motion-induced artifacts. Overall, these findings establish a scalable and mechanistically grounded platform for developing new Ex-ratiometric tools and provide a broadly applicable strategy for sensitive detection of neuropeptide dynamics in living systems.

neuroscience↗

bioRxiv2026

NSD2 deficiency disrupts the epigenetic landscape of cochlear hair cells to enhance ECM expression and to perturb cochlear hair cell function

Mammalian cochlear hair cells (HC) are crucial for hearing, and histone modifications may play an important role in HC maturation and functions. However, whether and how NSD2, a histone H3 lysine 36 (H3K36) dimethyltransferase, affects cochlear HC maturation remains unclear. Here, we established an HC-specific Nsd2 knockout mouse model and discovered that the loss of NSD2 results in severe structural defects in stereociliary bundles and profound hearing impairment. Integrated multi-omics profiling revealed that NSD2 deficiency leads to a decreased expression of H3K36me2, which in turn alters genome-wide chromatin accessibility and gene expression. Mechanistically, NSD2 deficiency triggers the aberrant upregulation of extracellular matrix (ECM) genes at the transcriptional level, causing excessive collagen accumulation and compromising tissue structure. Crucially, ECM intervention can mitigate NSD2-deficiency mediated hearing damage. Our study reveals an epigenetic mechanism by which NSD2 regulates cochlear HC maturation through inhibition of chromatin remodeling-induced ECM accumulation, and provides a potential new therapeutic direction for hearing impairment.

cell biology↗

bioRxiv2026

Reaction-aware hypergraph learning of chemical representations with LARK

Molecular pretraining offers a route to learning transferable chemical representations from unlabelled data. However, existing approaches pretrained on isolated molecular structures struggle to generalize to reaction-specific tasks because their pretraining objectives provide limited information about chemical transformations. A key challenge is to integrate this reaction information into chemical representations. Here we introduce LARK, a unified framework for learning atom-molecule-reaction knowledge from chemical transformations. Using approximately 0.6 million reactions encompassing 0.88 million unique molecular components, LARK combines bidirectional bond-electron reconstruction with structural and geometric supervision through a role-aware hierarchical hypergraph Transformer that links local atom representations to reaction context. The learned representations transfer to both reaction prediction and single-molecule property prediction, with strong performance across 42 tasks covering reaction outcomes, physicochemical properties, toxicity, metabolism and pharmacokinetics. Reactioncentre analyses show that LARK identifies where bonds break and form, while targeted interventions reveal that the learned atom representations contribute to reconstructing these changes. These findings indicate that LARK learns chemically informative representations of substructures involved in molecular transformations. Together, the results establish chemical transformations as a source of structured supervision for representation learning across molecular and reaction scales.

bioinformatics↗

bioRxiv2026

The RNA modification N6-methyladenosine restrains SIRPα to license myeloid efferocytosis in atherosclerosis

Background: Macrophages participate in atherosclerotic plaque development, progression and resolution, integrating lipid and inflammatory cues to balance tissue damage and repair. Despite considerable understanding of macrophage function in atherosclerosis, the underlying regulatory mechanisms governing these responses continue to evolve. Emerging evidence implicates epitranscriptomic gene regulation by the RNA modification N6-methyladenosine (m6A) in control of context specific immune responses, but its role in atherosclerosis is not well-defined. Methods: We integrated m6A quantitative trait loci (m6A QTLs) with Coronary Artery Disease (CAD) GWAS summary statistics. Using Oxford Nanopore direct RNA sequencing and MeRIP-seq, we constructed a high-resolution map of m6A modifications in macrophages. To determine the functional consequences of myeloid m6A loss in-vivo, we generated a myeloid-specific loss-of-function mouse model of m6A (Mettl14f/f LysMCre) and performed atherosclerosis studies using bone marrow transplantation into irradiated Ldlr-/- mice. Atherosclerosis lesions were analyzed using light microscopy and immunofluorescence imaging, with complementary in-vitro mechanistic studies performed in murine bone marrow derived macrophages (BMDMs). Results: m6A quantitative trait loci (m6A-QTLs) were enriched in CAD GWAS loci relevant to immune and lipid function, implicating m6A regulation in human CAD genetics. Using Oxford Nanopore direct RNA sequencing in conjunction with public MeRIP-sequencing data, we generated a single-base resolution, stoichiometric map of m6A modification in macrophages, nominating genes central to macrophage biology in atherosclerosis as high-confidence m6A targets. Myeloid specific deletion of the m6A "writer" complex subunit Mettl14 drove the development of larger, more necrotic and unstable atherosclerotic plaques on an Ldlr-/- background compared with Mettl14f/f controls, establishing an atheroprotective role for myeloid m6A. Loss of myeloid Mettl14 impaired macrophage efferocytosis in atherosclerotic plaques, in a dexamethasone-induced apoptosis in the thymus and in-vitro. Molecularly, m6A methylation of the "don't eat me" antiphagocytic receptor SIRP RNA suppressed its protein expression. Conclusions: These findings identify the myeloid m6A - SIRP axis as a novel homeostatic regulator of efferocytosis and establish epitranscriptomic remodeling as a crucial layer of macrophage regulation in atherosclerosis.

physiology↗