Biology subjects

Sun, C.

Publications and source records attributed to Sun, C..

At least 55 records · Page 3Linked to original sources

bioRxiv2026

FOXA1 preserves cell polarity and restrains lysosome biogenesis in non-small cell lung adenocarcinoma

BackgroundThis study investigates the role of the pioneer transcription factor FOXA1 as a master gene in sustaining epithelial cell polarization in early-stage lung adenocarcinoma. The partial loss of FOXA1 is explored to determine if it will affect plasticity and progression of lung adenocarcinoma. The study also addresses the transcriptional circuitry that links polarity defects to lysosome homeostasis. MethodsA multiomics approach was used to define the status of the chromatin in epithelial and mesenchymal states of A549 adenocarcinoma cells obtained with a newly synthetized TGF-{beta} receptor inhibitor or TGF-{beta} respectively. The study leveraged ATAC-seq, RNA sequencing, Cut&Tag sequencing of FOXA1 and histone marks profiling. The functional impact of FOXA1 was examined by partial silencing in vitro and by heterozygous FOXA1 deletion in a KrasG12D mouse model. Three-dimensional organoid culture, high-resolution electron microscopy, spatial transcriptomics and multiplex immunohistochemistry assessed carcinoma cell polarity, proliferation, the tumor microenvironment and organelle content. Group differences were evaluated with two-tailed t tests or one-way analysis of variance. ResultsFOXA1 binding and expression were highest in cells harboring an epithelial phenotype. In mouse KrasG12D LUAD tumors FOXA1 marked polarized, CDH1-positive cells; heterozygous loss diminished CDH1, disrupted apical-basal architecture, lowered organoid-forming efficiency and remodeled the immune microenvironment. Spatial transcriptomics and ultrastructural analyses showed that FOXA1-deficient carcinoma cells accumulated lysosomes, down-regulated vesicle fusion genes of the SNARE family and activated the lysosomal CLEAR gene network. FOXA1 occupied enhancers of lysosome-associated genes and competed with the transcription factor TFE3, thereby suppressing transcription of cathepsin B and cathepsin C and restricting lysosome biogenesis. ConclusionsFOXA1 is a central regulator that preserves epithelial cell polarity and limits lysosome formation in lung adenocarcinoma. Targeting the FOXA1-TFE3-lysosome axis may affect tumor plasticity and provide new therapeutic opportunities.

cancer biology↗

bioRxiv2026

Aberrant retinal structure and vasculature in mouse models of dominant retinopathies caused by CRX homeodomain mutations

CRX is a transcription factor essential for photoreceptor differentiation and functional development. Two missense mutations in CRX homeodomain, CRXE80A and CRXK88N, are linked to early-onset dominant retinopathies. Molecular studies have revealed distinct profiles of perturbed gene expression in differentiating photoreceptors of knock-in mouse models, resulting from altered DNA binding activities of mutant CRX proteins. This study characterizes concurrent retinal and vascular alterations in knock-in mouse models. Fated cones are present in heterozygous and homozygous CrxE80A and CrxK88N mutants at birth, but subsequent cone differentiation is rapidly compromised. Expression of rod marker rhodopsin (RHO) is absent in CrxK88N/Nretinae but present in other mutants through adulthood. Notably, as compared to wildtype controls, RHO expression is prematurely activated in neonatal CrxE80A mutants. Among tested mutants, only CrxE80A/+retinae elaborate rod outer segments but still lose visual function by young adulthood. The presence of irregular retinal rosettes is a striking pathological phenotype in all mutants. Retinal rosettes displace the localization of inner neurons without affecting their cell numbers during retinal development. Retinal vessels develop close contact with rosette structures. In summary, disrupted photoreceptor differentiation leads to the loss of visual function and formation of retinal rosettes. The presence of retinal rosettes secondarily impairs the localization of inner neurons and vasculature. A deeper understanding of these cellular underpinnings will inform pathogenesis of CRX homeodomain mutations.

neuroscience↗

bioRxiv2026

A Protein Language Model Reveals Organellar Calcium ATPases at Neuronal Synapses

The synapse between neurons hosts the protein machinery for information transfer and storage in the brain. Its local proteome, however, contains many proteins with unclear roles for synaptic function. To glean hypotheses from this local proteome, we developed Synapse Gigamapper (SyGi), a protein language model for predicting protein localization at synapses. SyGi identified 152 amino-acid motifs that are indicative of localization at excitatory or inhibitory synapses and revealed >100 candidate constituents from key cellular pathways. Among these candidates is the endoplasmic reticulum (ER)-bound ATPase for cytosolic Ca2+ clearance, SERCA. We found clusters of SERCA copies at excitatory synapses without ER. Rather, SERCA is colocalized with compartment-specific organelles at synapses-- the spine apparatus and synaptic vesicles. Taken together, SyGi is useful for exposing hidden components of neuronal synapses.

neuroscience↗

bioRxiv2026

STCS: A Platform-Agnostic Framework for Cell-Level Reconstruction in Sequencing-Based Spatial Transcriptomics

Sequencing-based spatial transcriptomics technologies, including Visium HD and Stereo-seq, now enable transcriptome-wide profiling at subcellular resolution. However, these platforms generate measurements over spatially barcoded units rather than biologically segmented cells, creating a fundamental bottleneck for cell-centric analysis and interpretation. Robust recon-struction of coherent single-cell transcriptomes from high-density spatial bins remains an unresolved computational challenge. Here we present STCS (Spatial Transcriptomics Cell Segmentation), a platform-agnostic framework that reconstructs cell-level gene expression profiles by integrating nuclei segmentation with a joint transcriptomic-spatial distance model. STCS is governed by two interpretable parameters and incorporates a reference-free parameter selection strategy based on internal stability and spatial coherence metrics, enabling adaptable deployment across tissue types and technologies without requiring matched ground-truth annotations. We benchmark STCS on a Visium HD human lung cancer dataset with matched Xenium-derived cell segmentation, enabling direct cell-level validation, and on high-resolution Stereo-seq mouse brain data to assess cross-platform generalizability. Across multiple evaluation dimensions--including cell-type agreement, spatial organization, gene-expression fidelity, and compositional accuracy--STCS achieves consistent improvements over existing methods while preserving biologically coherent spatial structure. As sequencing-based spatial transcriptomics is rapidly adopted across biomedical research, STCS provides a broadly applicable and open-source solution for reconstructing cell-resolved transcriptomes, facilitating more reliable downstream analyses and cross-platform integration.

bioinformatics↗

bioRxiv2026

Sex-specific Genetic Regulatory Effects in Chickens

Sexual dimorphism is a defining vertebrate feature, yet its sex-specific molecular architecture remains poorly understood. Here we established a sex-balanced, uniformly reared chicken cohort to map this landscape, integrating individual whole-genome sequencing with 7,969 bulk and 779,380 single nucleus transcriptomes across 32 tissues from 280 birds. We identified 495,098 independent expression quantitative trait loci for 20,194 genes, including 10,937 loci modulated by cell-type composition. Notably, 340 genes were regulated by 449 loci in a sex-dependent manner, significantly enrichment in endocrine tissues like adipose and the adrenal gland. Furthermore, we fine-mapped 1,219 structural variants, demonstrating their unique roles to tissue- and sex-specific expression beyond SNPs. Ultimately, we showed the utility of these regulatory effects in elucidating the molecular basis of metabolism and complex traits in both chickens and humans. This comprehensive atlas of regulatory effects provides profound insights into the genomic and molecular basis of sexual dimorphism in vertebrates.

genomics↗

bioRxiv2026

Preclinical CRX augmentation therapies for CRX-associated autosomal dominant cone-rod dystrophies

Cone-rod dystrophies (CoRD) are inherited retinal diseases (IRDs) with variable ages of onset, characterized by the progressive loss of cones, followed by secondary degeneration of rods. Cone-rod homeobox (CRX) is a transcription factor that regulates gene expression essential for photoreceptor development and maintenance. Mutations in CRX gene, including CRXE168d2 and CRXE80A, are implicated in autosomal dominant CoRDs. Although these mutations show distinct pathogenic mechanisms, published studies in knock-in mouse models have suggested a common treatment strategy: increasing WT CRX expression to reduce the detrimental activities of mutant proteins. This study employs two independent strategies of CRX augmentation to evaluate their therapeutic potential in CrxE168d2/+ and CrxE80A/+ mouse models. The Tet-On-hCRX transgenic system, a platform of proof-of-principle gene therapy, induces consistent and pan-photoreceptor expression of CRX augmentation in diseased retinae, allowing for the faithful assessment of functional and behavioral recovery. AAV-mediated CRX augmentation confirms the biosafety, delivery efficiency and efficacy of viral transduction in diseased retinae. Both strategies have achieved significant treatment outcomes in cone photoreceptor survival and overall photoreceptor functions in young adulthood. Treated cones survive past the age point of complete cone loss in untreated controls of both models. Treated rods show functional improvement and long-term survival through later adulthood. This preclinical study establishes valuable treatment regimens and benchmarks for CRX augmentation in the treatment of CRX-associated IRDs, and offers new insights into the mechanisms for photoreceptor development and survival.

neuroscience↗

bioRxiv2026

Volumetric montaging of optical coherence tomography in human retinas

Optical coherence tomography (OCT) has transformed clinical eye care by providing high-resolution volumetric imaging of the retina. Recently, ultrawide-field-of-view (FOV) OCT played an increasingly significant clinical role; however, most clinical OCT systems offer only a rather limited FOV. We increased the FOV of clinical OCT by volumetrically montaging multiple OCT datasets in three dimensions (3D). We performed volumetric montaging by representing the internal limiting membrane (ILM) and retinal pigment epithelium (RPE) in each volume as point clouds and using these point clouds to compute transformations that map each volume to a common reference frame. We validated our methodology using datasets from three institutions with different OCT hardware and data-acquisition procedures. Using the mean surface distance between point clouds, we found the error in montaging was less than the lateral pixel size. Our method enabled existing clinical OCT to achieve ultrawide FOV imaging without any hardware modification.

bioengineering↗

bioRxiv2026

Multimodal Behavior Scoring quantifies depression-like severity across chronic stress models and identifies stress-resilient mice

IntroductionRodent chronic-stress models are central to preclinical depression research, yet behavioral phenotypes are often assessed assay-by-assay, which can reduce cross-cohort comparability and mask heterogeneity across symptom domains (e.g., anhedonia, anxiety-like behavior, and behavioral despair). An integrative behavioral index may provide a more robust and interpretable measure of overall stress-induced severity and facilitate stratification of susceptible versus resilient individuals. MethodsWe developed the Multimodal Behavior Scoring (MBS) algorithm to integrate outcomes from standard assays--sucrose preference test (SPT), open field test (OFT), and forced swim test (FST)--into a unified severity score. MBS was evaluated in two independent paradigms, chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS), quantifying group discrimination, reproducibility (intraclass correlation coefficient, ICC), and phenotypic stratification. ResultsMBS robustly separated stressed from control mice (CUMS: +39.8%, p<0.0001; CSDS: +121.8%, p<0.0001) and showed high cross-cohort reproducibility (ICC>0.88). MBS further identified stress-resilient subpopulations and uncovered paradigm-specific behavioral signatures, with despair-dominant patterns in CUMS (FST-MBS, r=0.61) and anxiety-centric patterns in CSDS (OFT-MBS, r=-0.74). Excluding TST did not reduce discrimination performance. ConclusionMBS provides an integrative framework for quantifying depression-like behavioral severity and heterogeneity, enabling streamlined protocols and improving the translational utility of preclinical cohorts for biomarker discovery and antidepressant screening.

animal behavior and cognition↗

bioRxiv2026

A dual-factor complex governs archaeal ribosome hibernation by sensing energy status

Efficient coupling of cellular energy status to ribosome regulation is fundamental for cellular survival. Here, we identify the Archaeal Ribosome regulatory Complex (ARC)--a previously uncharacterized dual-factor complex comprising ARC-P and ARC-A. Cryo-EM reveals that ARC anchors to the small ribosomal subunit, establishing a stringent blockade of the tRNA and mRNA paths via an electrostatic wedge mechanism. This hibernation state is modulated by energy status: the complex remains stably associated under low-energy conditions, whereas ATP binding triggers rapid mobilization. Genetic analyses demonstrate that ARC acts as a translational brake essential for preserving ribosomal structural integrity, with ARC-A serving as the primary inhibitory factor. Notably, while the loss of ARC accelerates growth, it impairs recovery in proportion to stress severity. Phylogenomic analysis identifies ARC as an evolutionarily novel and widely distributed dual-factor system, revealing a conserved regulatory strategy for metabolic-translational coupling across diverse archaea. Our findings define a fundamental strategy where modular complexes integrate metabolic sensing with mechanical sequestration to balance growth and persistence.

biochemistry↗

bioRxiv2026

Quantitative Full-length transcriptome analysis by nanopore sequencing with Error-Aware UMI mapping

Comprehensive transcriptome profiling is essential for understanding RNA diversity and regulation, yet accurate identification and quantification of full-length transcript isoforms remain challenging with short-read sequencing technologies. Nanopore sequencing enables direct sequencing of long cDNA molecules and thus offers a powerful solution for full-length transcriptome analysis, but its application to quantitative transcriptomics is limited by PCR amplification bias and the difficulty of unique molecular identifier (UMI) recognition under high sequencing error rates. Here, we developed UMImap, a dedicated pipeline for robust UMI identification, error correction, and deduplication in nanopore data. By integrating transcript-aware UMI correction with long-read isoform assembly, UMImap substantially improves UMI recognition accuracy compared with existing methods and effectively mitigates PCR-induced duplication bias. Using this framework, we identified tens of thousands of full-length transcript isoforms, including a large fraction of previously unannotated isoforms that are significantly longer than reference annotations. Quantitative analyses demonstrate the reliability of UMImap for transcript-level quantification. Functional and pathway enrichment analyses of highly expressed novel isoforms revealed coherent and biologically meaningful patterns, including strong enrichment in RNA processing, splicing, and translation pathways. Our results establish UMImap as an effective solution for UMI-based quantification in nanopore full-length transcriptome sequencing and highlight the potential of long-read sequencing to simultaneously achieve accurate isoform discovery and expression analysis in complex transcriptomes.

bioinformatics↗

bioRxiv2026

A novel anaerobic n-Hexadecane hydroxylation pathway in Thermalkanevorax longiformis gen. nov., sp. nov. isolated from a deep-sea hydrothermal vent

Hydrothermal systems contain a wide spectrum of alkanes derived from biological sources and geological processes. However, despite their widespread occurrence in hydrothermal environments, the capacity and mechanisms of anaerobic alkane degradation by members of the phylum Bacillota remain poorly understood. In this study, we isolated a bacterial strain (designated strain L01) from the Lost City hydrothermal field (LCHF) by adding crude oil for enrichment culture. Strain L01 can grow anaerobically at 55 {degrees}C and pH 7.0 in medium supplemented with n-hexadecane, indicating its capability for anaerobic alkane degradation. Phylogenetic analysis based on the 16S rRNA gene sequence (93.11% similarity to its closest described relative) and average amino acid identity (AAI, 66.27-66.58%) revealed that strain L01 represents a novel genus within the family Symbiobacteriaceae, for which the name Thermalkanevorax longiformis gen. nov., sp. nov. is proposed. Cells of strain L01 are elongated rods measuring approximately 10-20 m in length and [~]0.2 m in diameter. Integrated genomic, transcriptomic, and metabolomic analyses revealed a previously unrecognized anaerobic n-hexadecane utilization pathway, involving initial alkane activation by AhyA homologous enzymes followed by stepwise oxidation and {beta}-oxidation. Together, these findings provide new insights into anaerobic alkane metabolism by hydrothermal bacteria, expanding current understanding of microbial hydrocarbon degradation in extreme marine environments. IMPORTANCEAlthough alkanes have be reported degradation by microorganisms through both aerobic and anaerobic metabolic pathways in hydrothermal ecosystems, the mechanisms underlying anaerobic alkane degradation remain incompletely understood, and the metabolic strategies employed by hydrothermal microorganisms are still poorly characterized. In this study, a novel genus bacterium Thermalkanevorax longiformis within the Symbiobacteriaceae family was isolated from the LCHF and identified an unrecognized C1-position n-hexadecane hydroxylation of AhyA homologous proteins at the anaerobic condition. These findings not only provide fundamental insights into the metabolic strategies of hydrothermal bacteria but also expand our understanding of microbial hydrocarbon degradation in extreme marine environments, offering a potential genomic resource for biotechnological applications in hydrocarbon remediation.

microbiology↗

bioRxiv2026

Innate immune sensing via the cGAS-STING pathway restricts extrachromosomal DNA-driven tumorigenesis

Extrachromosomal DNAs (ecDNAs) are circular DNA fragments frequently found in human cancers, where they amplify oncogenes, drive tumor heterogeneity, and promote therapy resistance and poor prognosis. Despite their prevalence, how ecDNAs interact with the immune system remains poorly understood. Here, we show that the cytosolic DNA sensor cGAS detects ecDNA fragments in the cytoplasm and activates the innate immune response. cGAS and STING are frequently silenced in ecDNA+ tumors through promoter hypermethylation. Restoring cGAS or STING in human and murine ecDNA+ cancer cells reactivates innate immune signaling and selectively suppresses ecDNA+ tumor growth in an immunocompetent mouse model. Using two ecDNA biogenesis models, we show that the cGAS-STING pathway restricts de novo ecDNA formation. Together, our findings identify innate immune sensing as a natural barrier to ecDNA-driven oncogenesis and establish cGAS-STING reactivation as a therapeutic strategy for ecDNA+ cancers. HighlightsO_LIThe cGAS-STING pathway is frequently silenced in ecDNA+ tumors C_LIO_LIRestoration of cGAS in ecDNA+ cells activates innate immune responses C_LIO_LIcGAS expression suppresses ecDNA+ tumor growth in vivo C_LIO_LIThe cGAS-STING pathway restricts de novo ecDNA biogenesis C_LI

cancer biology↗

bioRxiv2025

Thalamocortical coupling and cortical E-I balance generate diverse anesthetic α-spindles for interpretable EEG decoding

The neuronal circuits generating frequency (8-13Hz) oscillatory patterns during anesthesia are poorly understood, making their use difficult in predictive medicine. Here, we combine large-scale in vivo recordings of thalamocortical neuronal ensembles in anesthetized mice with a minimal neural mass model. We report non-rhythmic, weakly synchronized firing of thalamic and cortical neurons correlated with oscillatory patterns, indicating an emergent network rather than cellular dynamics. The associated imbalance between the firing of excitatory and inhibitory cortical neurons, together with an increase in firing fluctuations, favors larger amplitudes oscillations, whereas changes in thalamic neuron output control oscillation frequency. A neural mass model, comprising reciprocally connected excitatory and inhibitory cortical and thalamic neurons well reproduces the oscillation patterns observed in vivo at increasing anesthetic doses. These results provide a direct link between EEG oscillations during anesthesia and their underlying network/cellular dynamics which are well captured by a computational model that is clinically relevant for anesthetized brain state monitoring. HighlightsO_LI transient patterns during anesthesia emerge from thalamocortical and cortical excitatory-inhibitory (E-I) network dynamics. C_LIO_LI pattern frequency and amplitude reflect depth of anesthesia, dynamic thalamocortical equilibrium and E-I imbalance. C_LIO_LIEmergence of spindle-like patterns at multiple frequency defines newly characterized brain-state during anesthesia C_LIO_LIA mass-model reproduces the transient nature and spectral diversity of anesthetic-induced oscillations, linking neural circuit mechanisms to EEG output. C_LI

neuroscience↗

bioRxiv2025

Elucidation and engineering of arabinofuranosyltransferase to enable total de novo biosynthesis of paris saponins in yeast

Paris saponins (PSs) are structurally complex steroidal saponins that, due to their diverse glycosylation patterns, exhibit a range of significant pharmacological activities, including anti-tumor and antibacterial effects. However, incomplete characterization of the key enzymes responsible for glycosylation modifications has hindered their efficient heterologous biosynthesis. In this study, we reprogrammed the sugar donor specificity of a steroidal rhamnosyltransferase (UGT93M3) to enable the transfer of arabinofuranose (Araf). Through structural analysis, we identified key amino acid residues (368H/Q) that play an important role in determining Araf donor specificity. Guided by this insight, we successfully reconstructed the paris saponin I (PSI) biosynthetic pathway in Saccharomyces cerevisiae using engineered enzymes. To address challenges related to donor availability, we introduced UDP-sugar biosynthetic modules (UDP-Rha and UDP-Araf) into yeast. With this integrated platform, we were able to de novo produce a range of paris saponins, including diosgenin-3-O-glucosyl-(1[->]6)-glucoside (DGG), diosgenin-3-O-rhamnosyl(1[->]2) [glucosyl(1[->]6)]glucoside (DRGG) and paris saponin II. This work establishes a novel microbial platform for the sustainable production of paris saponins, particularly PSI, advancing the biosynthesis of steroidal glycosides and providing a potential strategy for the industrial-scale production of bioactive saponins. TeaserIn this study, we report the first complete de novo biosynthesis of four bioactive PSs, PSI, PSII, DGG and DRGG, in Saccharomyces cerevisiae from simple carbon source. Key advances include: (i) A single amino-acid switch (N368H) in the rhamnosyltransferase UGT93M3 endowed high-efficiency transfer of the rare five-membered arabinofuranose, solving a bottleneck in PS I biosynthesis; (ii) Elucidation of the molecular basis for sugar-donor specificity through AlphaFold3 docking and 300-ns molecular-dynamics simulations, revealing a histidine "latch" that stabilizes UDP-Araf in the catalytic pose; (iii) Construction of a 16-gene yeast chassis that integrates plant P450s, optimized glycosyltransferases, and de novo modules for UDP-rhamnose and UDP-arabinofuranose supply, achieving de novo microbial production of PS II, DGG, DRGG and PS I from glucose alone.

synthetic biology↗

bioRxiv2025

Organosulfur cycling in the multi-partner symbiosis between lucinid bivalves, sulphur-oxidizing symbionts, and Endozoicomonas

Organosulfur compounds play an important role in chemotaxis, stress protection, and nutrition in many marine symbioses. Lucinidae, an ancient and species-rich family of marine bivalves, host chemosynthetic sulphur-oxidising bacteria within gill epithelial cells, and is well-known for its contribution to inorganic sulphur cycling in marine sediments worldwide. Little is known about organosulfur transformations by lucinid-associated microbiota or the hosts potential contribution. Here, we integrated field measurements, genomics, transcriptomics, and experimental assays to investigate organosulfur cycling in three lucinid species from temperate and tropical environments. Concentrations of the osmolyte dimethylsulphoniopropionate (DMSP) in lucinids were typically much higher than in their surrounding environment, and varied with host species and season, but not with symbiont abundance. Indeed, candidate DMSP synthesis DSYB genes were expressed by the animal hosts implying that the host may be the source of DMSP. Furthermore, a newly identified and isolated Candidatus Endozoicomonas endolucinida symbiont was capable of DMSP catabolism to dimethylsulphide (DMS), which could be further syntrophically oxidised by the sulphur-oxidising symbionts that encode methanethiol oxidase genes in their genomes. Finally, incubation experiments supported a combined role of the host and its associated microbiome in organosulfur cycling during stress, with the highest DMSP concentrations measured when holobionts were incubated with antibiotics under anoxic conditions. This study identified a previously unrecognised microbial partner in lucinid symbioses and revealed its potential organosulphur-based metabolic interactions with both the host and the sulphur-oxidising symbionts, highlighting the capacity of these widespread associations to influence global organosulfur cycling.

ecology↗

bioRxiv2025

Isolation of the first cultured representative from a deep-branching phylum in serpentinite-hosted ecosystems

Serpentinization drives abiotic synthesis of organics (e.g., hydrocarbon) potentially conducive to the emergence of life, making serpentinite-hosted systems and associated microbial community key windows into nature of lifes origin. Although cultivation-independent studies uncovered the Candisdatus Bipolaricaulota widely distributed in serpentinizing environments, cultivation of this phylum has been unsuccessful. Here we cultured the first pure strain, J31, of Ca. Bipolaricaulota from the Lost City hydrothermal field, a well-characterized marine serpentinite system, using hydrocarbons as the primary nutrient source. As an early-branching bacterial lineage, strain J31 exhibits an unusual morphology composed of a central rod and elongated Toga-like extensions at both ends, and divides by binary fission. Strain J31 absorbs hexadecane through Toga ends via coordinated processes resembling inhalation and swallowing, after which hexadecane is efficiently transported to the central rod in the vesicle-like structures and subsequently converted into membrane lipids to support Toga synthesis and cellular growth. Hydrocarbon-degrading capability is widespread among the globally distributed members of Ca. Bipolaricaulota. Strain J31 colonizes serpentine minerals, facilitating the utilization of hydrocarbons derived from serpentines and promoting the release of soluble iron and silicon, thereby linking microbial activity to geochemical cycling. Thus, our study presents a novel strategy for cultivating deep-branching bacteria and offers insights into the metabolic foundations of early life on Earth--and potentially on other rocky planets undergoing serpentinization.

microbiology↗

bioRxiv2025

Microbial metabolism of complex organic matter across diverse deep-sea ecosystems

The deep sea is home to a vast and largely unexplored microbial biosphere, along with significant amounts of complex organic matter (COM). However, the ability of deep-sea microbes to metabolize complex organic matter across diverse regions remains poorly understood. Here, we combine 16S rRNA gene amplicon sequencing, metagenomics, and metatranscriptomics to comprehensively characterize prokaryotic communities across different years and habitats (cold seeps, hydrothermal vents, and seamounts). Our results reveal spatio-temporal community heterogeneity driven by geochemical gradients, alongside widespread genomic and transcriptomic potential for COM metabolism. Notably, the PVC (Planctomycetota-Verrucomicrobiota-Chlamydiota) superphylum exhibits extensive polysaccharide degradation capabilities, with Planctomycetota strain WC338 and Lentisphaerota strain WC36 isolated via laminarin enrichment. Growth and transcriptome data confirm their obligate laminarin dependence and robust degradation capacity, employing distinct enzymes (GH16 and GH2), whose broad distribution across diverse PVC superphylum lineages underscores their prevalence. Furthermore, we demonstrate that laminarin acts as a highly effective selective substrate for enriching and isolating the deep-sea PVC superphylum bacteria. Collectively, these findings delineate specialized adaptations within the PVC superphylum for polysaccharide degradation, significantly expanding our understanding of deep-sea microbial roles in global carbon cycling.

microbiology↗

bioRxiv2025

Sub-daily Bermuda Atlantic Time Series virus sampling reveals taxonomy, host, and functional differences at the population, but not community level

Ocean microbes contribute to biogeochemical cycles and ecosystem function, but they do so under top-down pressure imposed by viruses. While viruses are increasingly understood spatially and beginning to be incorporated into predictive modeling, high-frequency ocean virus dynamics remain understudied due to methodological challenges. Here we sampled stratified Bermuda Atlantic Time Series (BATS) waters for 112 hours at sub-daily 4-(surface) or 12-(deep chlorophyll maximum) hour intervals, purified viral particles from these samples, sequenced their metagenomes, and used the resulting data to characterize high-frequency virus community dynamics. Aggregated community diversity metrics changed with depth, but were not statistically significant temporally at a fixed location. However, finer-scale population-level analyses revealed both depth and temporal change, including physicochemical depth-driven differences and, in surface waters, thousands of viral populations that exhibited statistically significant diel rhythms. Statistical analyses revealed three main archetypes of temporal dynamics that themselves differed in abundance patterns, host predictions, viral taxonomy, and gene functions. Among these, highlights include viruses resembling an archetype with a night peaking pattern in activity that include an over-representation of viruses that putatively infect Prochlorococcus, a phototrophic cyanobacteria. Together, these efforts provide baseline community-and population-scale short-time-frame observations relevant to future climate state modeling.

microbiology↗