Biology subjects

Wang, S.

Publications and source records attributed to Wang, S..

At least 73 records · Page 4Linked to original sources

bioRxiv2026

A Tumor-Pituitary-Stromal Axis Promotes Colorectal Cancer Progression

Peripheral tumors can reprogram systemic physiology, yet how they engage central endocrine organs to remodel the local tumor microenvironment is unknown. We found that colorectal cancer (CRC) elevates circulating BMP2, which activates pituitary signaling and enhances endocrine output. Increased pituitary-derived growth hormone acted on growth hormone receptor-expressing cancer-associated fibroblasts (CAFs), inducing a p21-dependent senescence-like state and tumor-promoting secretory program. Disruption of pituitary BMP signaling or fibroblast GHR reduced tumor growth, whereas fibroblast-specific depletion of p21 abrogated GHR-dependent tumor promotion. In patients with CRC, elevated pituitary metabolic activity correlated with stromal p21 expression and tumor burden. Our study reveals a tumor-pituitary-stromal signaling axis through which a peripheral malignancy recruits a central endocrine organ to remotely shape its own microenvironment and promote disease progression.

cancer biology↗

bioRxiv2026

TLS-Sim: An Open-Source Toolkit for Individualized Transcranial Light Stimulation Modeling with Deep-Learning-Accelerated Simulation

Background: Accurate modeling of photon transport through the heterogeneous tissues of the human head is important for individualized transcranial light stimulation (tLS). However, high-precision Monte Carlo (MC) simulations can be computationally demanding, and existing general-purpose simulation tools do not provide an integrated, brain-oriented workflow. Methods: We developed TLS-Sim, a framework that integrates subject-specific head-model construction, multiple light-source configuration, GPU-accelerated MC photon simulation, visualization, and intracranial dosimetric analysis. Its central feature is a deep-learning-accelerated MC pathway, termed Flux-to-Flux, that estimates a high-photon-count energy-deposition field from a paired low-photon-count simulation. Sparse and full Monte Carlo fields were encoded using a three-dimensional variational autoencoder (VAE), and a three-dimensional velocity network was trained to transform the sparse latent representation toward the corresponding full-simulation representation. Results: We demonstrate the end-to-end toolkit and the Flux-to-Flux (F2F) pathway on a representative individualized head model evaluated across three source configurations. Relative to the sparse simulation, the learned prediction improved agreement with the full Monte Carlo reference by approximately +4 dB in signal-to-noise ratio on average, with correspondingly higher structural similarity and lower mean absolute error. Conclusions: TLS-Sim provides a modular, openly released computational framework for individualized tLS simulation and analysis. The Flux-to-Flux pathway is presented as an implemented capability that reduces the computational burden of high-photon-count simulation while improving spatial agreement with the full MC reference, most strongly at the low-fluence field boundaries where the sparse simulation is noisiest.

bioengineering↗

bioRxiv2026

Non-contact optical imaging of tissue deformation enables in vivo cardiovascular monitoring

Significance: Continuous, non-invasive monitoring of cardiovascular physiology provides critical information for clinical decision-making and patient care. Emerging optical sensors enable non-contact measurement of physiological parameters such as heart rate and respiratory rate, but current methods are limited in their ability to capture spatially resolved physiological waveforms. Aim: We aimed to extend the capabilities of non-contact cardiovascular monitoring by using an imaging-based approach from which spatially resolved physiological waveforms can be extracted and cardiovascular biomarkers can be derived in vivo. Approach: We implemented a digital holographic imaging sensor to continuously measure calibrated tissue motion for in vivo assessment of cardiovascular biomarkers in six adult male Sprague-Dawley rats, with validation against electrocardiographic and invasive arterial blood pressure measurements. Results: Heart rate and pulse arrival time-derived pulse wave velocity calculated from digital holographic imaging demonstrate strong agreement with reference-derived metrics (concordance correlation coefficient [≥] 0.98). Heart rate variability shows moderate agreement with reference-derived metrics (concordance correlation coefficient [≥] 0.59).

bioengineering↗

bioRxiv2026

Dilatable DNA origami nanopores as nuclear pore mimics

The nuclear pore complex (NPC) is a massive protein system that controls all nucleocytoplasmic transport via a dynamic network of intrinsically disordered proteins called FG-Nups. We developed an NPC-mimicking DNA origami nanostructure that self-assembles into a tetrameric, octagonal nanopore with an inner diameter that, through addition of DNA oligonucleotides, can be tuned in a user-defined fashion from 57 to 66 nm - mimicking the contracted and dilated states of NPCs. We demonstrated that these origami nanopores can dilate within minutes and recontract at slower timescales. Both contracted and dilated pores can be inserted into lipid bilayers, where they maintain their conformation and allow transmembrane transport of fluorescent proteins. With outer diameters up to 87 nm, these are, to our knowledge, the largest DNA origami nanopores inserted into lipid membranes. Functionalization of the pores with the FG-Nup Nsp1 reduces non-specific cargo diffusion across the lipid membrane while facilitating translocation of the transport receptor Kap95, demonstrating transport selectivity much like biological NPCs. The work establishes a size-tunable platform to dissect nuclear transport mechanisms, with potential applications for engineering programmable artificial channels.

biophysics↗

bioRxiv2026

Neurokinin 1 receptor blockade is associated with increased survival of patients with C. difficile infection

Clostridioides difficile is a major cause of healthcare associated infections. C. difficile infection (CDI) is a toxin-mediated disease driven by the secretion of two large protein toxins, Toxin A (TcdA) and Toxin B (TcdB). TcdA and TcdB cause neurogenic inflammation that can contribute to intestinal inflammation in rat and mouse models. Substance P (SP), a potent vasoactive neuropeptide, is a major contributor to C. difficile toxin induced inflammation in animal models. SP acts on multiple receptors including the high affinity receptor NK1-R, and lower affinity receptors (Mrgprb2 and NK2-R). Through in vivo mouse infection models, we confirmed the effects of SP in hypervirulent C. difficile are largely mediated by the neurokinin-1 receptor (NK1-R), the high affinity receptor for SP. Through genetic mice that lack mast cells (cKitW-sh) we determined that mast cells which respond to SP in certain kinds of neurogenic inflammation appear dispensable for inflammation caused by C. difficile infection. We explored the role of NK1-R antagonists in a retrospective study of a large clinical cohort. We determined that, after propensity matching, NK1-R antagonists were associated with a significant survival benefit and that patients treated with NK1-R antagonists showed evidence of reduced vascular inflammation (increased serum albumin). Together these data suggest blocking SP activity through antagonism of NK1-R with small molecule inhibitors may be a useful strategy for adjunctive treatment during C. difficile infection.

microbiology↗

bioRxiv2026

The lncRNA Statera regulates synaptogenesis by repressing the retrotransposon copia in Drosophila

Retrotransposons are mobile genetic elements that can impair genome integrity, and their insertions and dysregulation have been implicated in various diseases. However, growing evidence suggests that retrotransposons may play important physiological roles. At the Drosophila larval neuromuscular junction (NMJ), the ViSyToR (Viral Synaptic Transfer of RNA) pathway requires the active retrotransposon copia as a key negative regulator of synaptogenesis. Here, we identify a long non-coding RNA, Statera (Stae), as a regulator of copia, initially discovered through its physical association with the Copia protein. Stae is highly expressed in the central nervous system and body wall muscles of Drosophila larvae. CRISPR knockout or RNAi knockdown of Stae leads to a general decrease of bouton number at the NMJ, indicating its role in promoting synaptogenesis. Furthermore, copia is highly upregulated in Stae mutants, suggesting that Stae functions to repress copia. Mechanistically, Stae reduces copia RNA stability and limits copia DNA copy number. Additional knockdown of copia in motor neuron-specific Stae RNAi animals rescues the abnormal NMJ morphology. Together, our findings reveal an unexpected role for a long non-coding RNA in promoting synaptogenesis by repressing a retrotransposon.

neuroscience↗

bioRxiv2026

Cortical Hierarchy Dynamically Organizes Large-Scale Neural Propagation

Flexible behaviour depends on the continuous coordination of sensory-driven and internally guided processing, yet whether the cortical hierarchy spanning lower-order sensory to higher-order association systems dynamically organizes large-scale cortical propagation over time remains unclear. Here we combined source-resolved magnetoencephalography with Riemannian cortical-flow modelling to derive hierarchy consistency, a moment-to-moment measure of the alignment between cortical propagation and the principal sensory-to-association functional gradient. We found that large-scale cortical propagation was dynamically organized by the cortical hierarchy. Hierarchy consistency exhibited a reproducible low-frequency periodic component that defined a characteristic timescale for the continuous updating of propagation direction. This dynamic organization was coordinated by a distributed cortical switchboard spanning the default-mode, salience, control and limbic systems, and was constrained by structural connectivity and network-control architecture. It flexibly adapted to behavioural demands, with hierarchy consistency increasing across both sensorimotor and working-memory states, while its characteristic periodicity shifted in a task-dependent manner. Moreover, hierarchy-related propagation dynamics were systematically reorganized across ageing and associated with higher-order cognitive function. Together, these findings establish the cortical hierarchy as a dynamic organizing principle that continuously shapes the direction and temporal evolution of large-scale cortical propagation to support adaptive behaviour.

neuroscience↗

bioRxiv2026

scRep: A Latent-Space Self-Distilled Foundation Model for Single-Cell Representation Learning

Single-cell foundation models have shown strong potential for learning transferable representations from large-scale transcriptomic data. However, many existing approaches rely on reconstructing masked gene expression values, creating a potential mismatch between observation-space reconstruction and the goal of learning stable biological representations. This challenge is particularly relevant to single-cell RNA sequencing, where sparsity, incomplete gene detection, and technical variation can obscure the underlying biological state. Here, we introduce scRep, a compact latent-space self-distillation framework for single-cell representation learning. Rather than reconstructing raw expression values, scRep aligns differently perturbed views of the same cell through a momentum-updated teacher--student architecture, with self-distillation objectives at both the cell and gene levels. This representation-centered formulation encourages the model to capture biological information that remains stable across incomplete and perturbed transcriptomic observations. Using frozen representations without task-specific fine-tuning, scRep pretrained on approximately 2.8 million cells achieves the strongest overall performance across the evaluated frozen-representation benchmarks, demonstrating strong sample efficiency. A larger-scale scRep model pretrained on 30.72 million cells further demonstrates that the framework remains effective when scaled to a substantially larger and more diverse corpus. Beyond cell identity, scRep prioritizes established marker genes, recovers transcription factor--associated gene programs with cell-type-specific activity, and preserves continuous developmental structure that supports graph-based pseudotime inference. We further show that pretraining performance is closely associated with biological diversity: reducing redundant cells while improving cell-type coverage can match or exceed the performance of larger, less balanced training corpora. Together, these results establish latent-space self-distillation as an effective alternative to expression reconstruction for single-cell foundation modeling and suggest that efficient scaling depends not only on the number of cells, but also on the learning objective and the biological diversity of the pretraining corpus.

bioinformatics↗

bioRxiv2026

Stomatal and xylem plasticity, not growth rate, determines white spruce resilience to warmer and drier climates

In a warmer and drier climate, forest productivity will depend on trees' ability to maintain carbon uptake and hydraulic function. Whether fast-growing genotypes of boreal conifers are more vulnerable to combined climatic stress remains uncertain. Using a full-factorial field experiment, we investigated how progressive soil drying combined with extended warming affects growth, xylem development, and photosynthesis in two Picea glauca families with contrasting growth strategies. Rainout structures first reduced soil moisture from 25% to 18%, followed by a +5{degrees}C warming treatment applied using infrared heaters. During the warmest and driest period in August, air temperature reached 34.5{degrees}C in the warmed plots, while soil moisture declined to a low of 15% in the combined rainout and warming treatment. Contrary to expectations, both fast- and slow-growing white spruce families exhibited similar resilience to concurrent warming and soil drying. This finding challenges the prevailing theory that faster growth increases vulnerability to climatic stress. Despite an approximately 50% reduction in rainfall, pre-dawn water potential remained above -0.5 MPa across treatments, reflecting that seedlings were able to avoid hydraulic stress. Although the fast-growing family maintained greater height and diameter growth compared to the slow-growing family, both exhibited similar physiological and anatomical responses to warming. Warming decreased stomatal conductance, which increased intrinsic water-use efficiency. Latewood xylem traits related to hydraulic efficiency were also reduced under warming. Together, these coordinated stomatal and xylem adjustments decreased water loss and protected hydraulic function, enabling both families to maintain high photosynthesis and growth under simulated climate conditions. Overall, white spruce exhibits strong phenotypic plasticity, supporting intraspecific resilience to moderate warming and soil drying representative of projected 21st-century summer conditions for central and eastern Canada.

plant biology↗

bioRxiv2026

Programmable Self-Assembly of RNA Nanostructures with >100 Unique Components

Sophisticated biomolecular functions often arise from large, precisely organized architectures, motivating efforts to construct increasingly complex structures through programmed nucleic acid self-assembly. Although RNA offers a richer repertoire of structural motifs and biological functions than DNA, RNA nanostructures constructed to date have remained substantially less complex and less scalable than their DNA counterparts, most notably DNA origami and DNA bricks, which rely on large libraries of synthetic single-stranded (ss) DNA strands. Directly adapting these strategies to RNA, however, faces two major barriers: (i) the high cost of producing large libraries of distinct synthetic ssRNA strands, and (ii) the limited stability of ssRNA under conditions commonly used for assembling multicomponent nucleic acid nanostructures. Here we present the double-stranded RNA (dsRNA) bricks approach, which addresses both barriers by adopting principles inspired by natural RNA systems: (i) many distinct RNA components ("bricks") are encoded within a single precursor transcript and released by enzymatic processing, (ii) each brick's predominantly double-stranded nature enhances stability. The resulting dsRNA bricks self-assemble through programmable branched kissing-loop interactions. Using this approach, we constructed complex two- and three-dimensional RNA nanostructures with more than 100 distinct components, representing, to our knowledge, the largest and most compositionally complex RNA nanoarchitectures reported to date. Overall, the dsRNA bricks approach establishes a scalable and robust framework for constructing complex RNA nanostructures with compositional and architectural sophistication approaching that of DNA-based systems, thereby opening new opportunities for programmable RNA materials and RNA-based devices.

synthetic biology↗

bioRxiv2026

Spatial-filtering nanoscopy for 40-nm label-free Raman imaging

Super-resolution fluorescence microscopy overcomes the optical diffraction limit and has significantly advanced our understanding of biological complexity within the framework of fluorescence labelling (1). Fluorescence labelling underpins this capability, enabling high photon budgets, superior signal contrast, and tuneable photophysical properties essential for diverse super-resolution modalities (2,3). In contrast, label-free Raman imaging offers intrinsic chemical specificity (4), supporting applications ranging from biomolecular fingerprinting to cell metabolic mapping (5-8) and histopathological tissue characterization (9,10). Despite its label-free advantage and chemical specificity, Raman imaging remains fundamentally limited in both spatial resolution and imaging contrast due to inherently low signal throughput and weak intrinsic Raman contrast (11-13). Here, we introduce spatial-filtering nanoscopy (SFN), a physics-driven super-resolution strategy that achieves resolution enhancement through targeted signal purification instead of signal amplification, offering a conceptually distinct pathway beyond the diffraction limit. SFN synergistically integrates a sub-millimetre microsphere lens (SMML) with a standard confocal Raman microscope, harnessing two complementary physical effects: (i) the photonic redistribution effect (PRE), which narrows the lateral excitation profile, and (ii) the three-dimensional spatial filtering (3D-SFE), which effectively suppresses both lateral and axial background. We demonstrate SFN-enabled super-resolution Raman imaging of silicon nanostructures, intact cells, and tissue sections, achieving an effective lateral resolution of approximately 40 nm, and chemically resolving subcellular features including organelles and pseudopodia without exogenous labels. These findings establish SFN as a broadly generalizable hardware-based super-resolution strategy, readily deployable on standard confocal platforms and extensible across diverse optical imaging modalities.

bioengineering↗

bioRxiv2026

The mitochondrial RNA extrusion-induced innate immunity is regulated by N6-methyladenosine machinery

Mitochondrial RNA (mtRNA) released into the cytosol functions as a damage associated molecular pattern that activates pattern-recognition receptor (PRR)-mediated inflammation, yet its release mechanisms and cytoplasmic fate remain poorly understood. Here we report that chemical Abt-373-treatment and Vesicular stomatitis virus (VSV) infection induce mtRNA extrusion through Bax/Bak and VDAC1 channels, accompanied by mtDNA release. Extruded mtRNA in A549 cells activates multiple cytosolic PRRs, including RIG-I, MDA5, TLR3/7/8, and PKR, each contributing differentially to the innate immune signaling. Analysis of GEO datasets and methylated RNA immunoprecipitation (MeRIP) assays further reveals that mtRNA carries methyladenosine (m6A) modification. m6A machinery proteins are involved in the cytoplasmic retention time of mtRNA and its interaction with RIG-I, thereby modulating mtRNA-induced innate immunity. Thus, our work establishes in vitro models of mtRNA extrusion, and highlights m6A-dependent modulation as a potential therapeutic target for mtRNA-driven inflammation.

immunology↗

bioRxiv2026

Dynamic Control of Prokaryotic Chromosome Ploidy Rewires Metabolic Networks to Enhance Product Biosynthesis

Building high-performance microbial cell factories requires dynamic coordination of resource allocation among cellular growth, target-product biosynthesis, and endogenous host metabolism. However, existing polyploid engineering strategies rely primarily on static manipulation of chromosome copy number. Although increasing gene dosage can enhance biosynthetic capacity, static designs cannot readily accommodate the changing metabolic demands encountered during fermentation. Here, we developed a metabolite-responsive dynamic polyploid engineering strategy that couples chromosome ploidy to the cellular metabolic state. We first constructed a high-performance L-threonine biosensor and used it to sense intracellular L-threonine levels and regulate ftsZ expression, a key cell-division gene, thereby establishing a dynamic polyploid system that requires neither exogenous inducers nor antibiotics. This system enabled engineered cells to progressively transition from polyploid to haploid during fermentation, accompanied by stage-specific remodeling of cellular physiology and metabolism. Physiological characterization revealed a marked increase in cell size and alterations in cell-envelope properties during the polyploid phase, followed by a gradual decrease in chromosome copy number as fermentation progressed. Transcriptomic and metabolomic analyses further demonstrated that dynamic ploidy transitions induced global metabolic network rewiring, remodeling the tricarboxylic acid cycle and amino acid metabolism while redirecting carbon flux toward the biosynthesis of aspartate-family amino acids. Ultimately, dynamic polyploid engineering substantially enhanced L-threonine production, enabling the engineered strain to achieve an L-threonine titer of 183.1 g/L and a yield of 0.67 g/g glucose in 5-L fed-batch fermentation without antibiotics or exogenous inducers. These findings show that dynamic regulation of chromosome ploidy can couple gene-dosage control with remodeling of cellular physiology and metabolic networks, providing a new engineering strategy to overcome the limitations of static polyploid designs and build high-performance microbial cell factories.

synthetic biology↗

bioRxiv2026

Programmable De Novo Design of Mesoporous Protein Crystal Frameworks

Three-dimensional protein crystals are ordered, porous macroscopic materials with potential applications in catalysis, biosensing, and biomedicine. However, most protein crystals are obtained by empirical screening, providing limited control over the lattice architecture, pore geometry or component composition that determine material function. Here, we present a modular strategy for the programmable design of highly porous, framework-like protein crystals using predefined protein-protein interactions. This strategy yielded over 30 distinct protein crystals, including single-component and multicomponent P213 and I213 lattices that grow to over 100 micrometers in size. Small-angle X-ray scattering and electron microscopy showed close agreement between experimental lattices and computational models. RFdiffusion-guided design generated isomorphous variants with matched lattice parameters, enabling coherent protein crystal alloys, epitaxial core-shell growth and reversible shell assembly. The designed crystals exhibit tunable mesoporous architectures, with limiting apertures of 2-18 nm, and support genetically encoded incorporation of fluorescent protein guests. These results establish a general route to programmable lattice engineering of protein crystals and position them as genetically encoded, compositionally tunable mesoporous materials.

synthetic biology↗

bioRxiv2026

Chromatin-Assisted Targeting Enables Precise DNA Methylation Editing in Plants

Precise installation of DNA methylation at selected loci offers a powerful strategy for regulating gene expression without altering DNA sequence, but existing plant epigenome editors are constrained by limited efficiency, locus dependence, and genome-wide off-target methylation. Here, we developed SunTag-MQ1v variants incorporating TRBIP1, which promotes removal of the antagonistic H3K4me3 mark, and CHLAMY, an oligomerizing alpha crystalline domain protein from Chlamydomonas reinhardtii. TRBIP1 enhanced methylation and silencing at the Arabidopsis FWA promoter but caused widespread off-target methylation and severe developmental defects. Adding CHLAMY produced SunTag-CHLAMY-TRBIP1-MQ1v (designated as SunTag-NOVA), which successfully overcame the lethality and widespread off-target effects associated with direct TRBIP1-MQ1v fusions. We demonstrate that CHLAMY drives higher-order oligomerization of the editing complex, which enhances target specificity and mitigates off-target accumulation. SunTag-NOVA robustly installed DNA methylation and repressed transcription at the endogenous FWA, FT and TMM genes with minimal genome-wide off-target consequences. These results show that combining local chromatin modification with controlled effector assembly can improve targeted DNA methylation, and establish SunTag-NOVA as a specific epigenome-editing platform for plants.

plant biology↗

bioRxiv2026

J-domain proteins bridge the PKL and ATRX complex to transcription factors to fine-tune gene expression via H3.3 deposition

Epigenetic modifications, including histone modifications and DNA methylation, direct gene expression programs during the growth and development of eukaryotic organisms. In Arabidopsis thaliana, the chromatin remodeler PICKLE (PKL), a homolog of animal CHD3, plays a critical role during these processes. Previous studies of PKL have painted a complex picture of its function, including both activating and repressive roles, however, how PKL can control both transcriptional silencing and activation is unknown. We have identified a group of J-domain-containing proteins (DNAJs), usually known for their roles in protein folding, that guide PKL recruitment to various gene promoters by bridging PKL to transcription factors. Mutation of PKL's DNAJ-interacting domain disrupts PKL association with chromatin. Once recruited to transcription factor-bound sites, PKL coordinates with the histone chaperone ATRX to deposit HISTONE3.3 (H3.3) at targeted loci, which also negatively affects the accumulation of H3 lysine 27 trimethylation (H3K27me3) at promoters. We found that transcriptional outcome of PKL binding depends not only on the changes in H3.3 occupancy but also on the pre-existing chromatin context at PKL-targeted sites. Our findings outline a new mechanism for CHD3 chromatin remodeler recruitment and function.

plant biology↗

bioRxiv2026

C1Q-associated adaptive myeloid remodelling accompanies early response to BCMA CAR-T therapy in multiple myeloma

BCMA-directed chimeric antigen receptor T cells induce deep responses in multiple myeloma, yet the immune ecology accompanying early response remains incompletely resolved. We reanalysed 171,971 single-cell transcriptomes from 25 peripheral-blood and bone-marrow specimens from ten patients. At day 30, responders showed concordant enrichment of C1Q and IFN-{gamma} programmes in blood and marrow myeloid pseudobulk profiles. Antigen-presentation genes were enriched in blood, whereas TGF-{beta} and hypoxia programmes were depleted in responding marrow. Cholesterol-efflux genes were not enriched in responders or after treatment. A composite C1Q-cholesterol score showed nominal associations with response and CD8 dysfunction in selected compartments, but none survived study-wide correction. The pathway results support an adaptive, antigen-presenting C1Q-associated programme rather than a uniformly suppressive C1Q macrophage model. This state-contingent interpretation of early myeloid remodelling requires prospective, patient-level validation before biomarker or causal claims are warranted.

immunology↗

bioRxiv2026

Public-Data Reanalysis Links MS4A4A to M2-like Human Myeloid States and Supports a Predicted Four-Pass Transmembrane Fold

Background/Objectives: MS4A4A is associated with M2-like macrophage states, while the MS4A gene cluster modifies soluble TREM2 levels and Alzheimer's disease risk. We asked whether MS4A4A consistently marks the M2 side of human myeloid activation and whether AlphaFold supports a proposed MS4A4A-MS4A6A interaction. Methods: We reanalysed four public human datasets: bulk RNA-seq and ATAC-seq of primary monocyte-derived macrophages from independent three-donor cohorts, and single-cell RNA-seq atlases of healthy liver and severe COVID-19 blood. MS4A4A and an MS4A4A-MS4A6A complex were modelled with AlphaFold 3 and evaluated using pLDDT, predicted aligned error, and ipTM. Results: MS4A4A was higher in M2 (IL-4) than in M1 (IFN-gamma; + LPS) macrophages in all three donors (log2 fold change +2.68, adjusted P = 0.0013). Its promoter showed the highest mean accessibility in M2. MS4A4A was macrophage-enriched in liver and monocyte-enriched in blood, and was detected in 76.7% of M2-like versus 39.3% of M1-like liver macrophages, with the difference driven mainly by the proportion of positive cells. AlphaFold confidently modelled the four transmembrane helices (mean pLDDT 83.1), but the predicted MS4A4A-MS4A6A interface was not supported (ipTM 0.59). Conclusions: MS4A4A is consistently associated with the M2 side of human myeloid activation across independent transcriptomic, chromatin, and single-cell datasets. The findings are associative, and the proposed MS4A4A-MS4A6A interface remains an untested structural hypothesis.

genomics↗