Biology subjects

Su, H.

Publications and source records attributed to Su, H..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Inflammatory memory disables a DDR1 degradation checkpoint to enable pancreatic cancer growth

Inflammation and stroma remodeling regulate pancreatic ductal adenocarcinoma (PDAC), but how or if these cues are integrated at the molecular level remains unclear. Here, we identify a metabolic checkpoint that controls the stability of the collagen receptor DDR1, and subsequent tumorigenesis. We show that defective Col-I remodeling deprives PDAC cells of the high affinity DDR1 ligand, [3/4]Col-I, resulting in reduced ATP and activation of AMPK. AMPK phosphorylates DDR1 at T519, promoting its recognition by the E3 ubiquitin ligase adaptor FBXW2 and subsequent degradation. Importantly, this degradation pathway can be disabled by inflammatory signaling. Exposure to inflammatory cytokines induces methylation-dependent silencing of FBXW2, which establishes an inflammatory memory that preserves DDR1 stability, enabling sustained ligand-triggered receptor oligomerization and downstream NF-{kappa}B-NRF2 signaling even in restrictive stromal environments. Together, these findings identify regulated receptor turnover as a mechanism through which stromal architecture, metabolic state, and inflammatory memory are integrated to control PDAC progression.

cancer biology↗

bioRxiv2026

GCN-Mamba: Graph Convolutional Network with Mamba for Antibacterial Synergy Prediction

The escalating crisis of antimicrobial resistance necessitates novel therapeutic strategies, among which drug combination therapy shows great promise by enhancing efficacy and reducing toxicity. However, identifying effective synergistic pairs from the vast combinatorial space remains experimentally challenging and resource-intensive. To address this, we introduce GCN-Mamba, a deep learning framework that integrates Graph Convolutional Networks (GCN) with the Mamba State Space Model. This architecture captures both local molecular topological structures and global implicit interactions by leveraging Extended 3-Dimensional Fingerprints (E3FP) and bacterial gene expression profiles. Evaluation on a comprehensive dataset demonstrated that GCN-Mamba significantly outperforms classical machine learning models in predictive accuracy. In a targeted case study against Methicillin-resistant Staphylococcus aureus (MRSA), the model successfully rediscovered known synergistic pairs, such as Quercetin and Curcumin, consistent with recent literature. Furthermore, prospective in vitro validation confirmed a novel synergistic combination of Shikimic acid and Oxacillin, validating the models practical utility. By efficiently prioritizing potential candidates, GCN-Mamba serves as a powerful and reliable tool for accelerating the discovery of synergistic antimicrobial combinations, effectively bridging the gap between computational prediction and experimental validation.

bioinformatics↗

bioRxiv2026

BABYBOOM-like expression in the cowpea egg and central cellenables parthenogenesis, endosperm development, and viable haploid seed formation

Introductory Paragraph (Nature Plants format)Parthenogenesis or fertilization-independent embryogenesis occurs at low frequency in sexual plants. Expression of BABYBOOM-like (BBML) and PARTHENOGENESIS (PAR) genes in the egg cell of several diploid dicot crops induce parthenogenesis at varying frequency; however, recovery of viable haploid seeds has rarely been reported, perhaps due to a lack of viable endosperm formation. In the legume cowpea (Vigna unguiculata L. Walp), ectopic egg cell expression of the endogenous BBML homolog (VuBBML1) and PAR from Taraxacum officinale induces parthenogenesis; however, seeds abort as endosperm formation is blocked following self-pollination. Expression of VuBBML1 in both the egg cell and central cell, together with central cell fertilization following self-pollination, results in viable seeds that germinate and give rise to haploid plants. VuBBML1 has a functional role in the formation of cowpea embryo and endosperm seed compartments. This finding opens possibilities for establishing double haploid production during homozygous parental breeding, and asexual seed induction for fixing hybrid vigor in cowpea.

plant biology↗

bioRxiv2025

Immunotherapy with Pro-regenerative Macrophages from Embryonic Stem Cells Ameliorate Osteoarthritis via TNFAIP3-Mediated Chondroprotection

Immune cell-based therapies for osteoarthritis (OA) remains underexplored. Macrophages coordinate tissue repair, yet their functional heterogeneity and therapeutic applicability, particularly for designed stem cell-derived populations with tailored reparative properties are not fully delineated. Inspired by embryonic skeletal development as a paradigm of scarless regeneration, we identified a pro-regenerative macrophage population through a single-cell RNA atlas of developing skeletal tissues. We subsequently established a mechanically dynamic induction approach to efficiently generate pro-regenerative macrophages from human embryonic stem cells (hESCs), mimicking this developmental phenotype. In vitro, these macrophages mitigate cartilage degradation in OA explants and suppress pro-inflammatory, catabolic signaling in chondrocytes. Injection into murine OA joints robustly attenuates disease progression, reduces extracellular matrix breakdown, and resolves synovial inflammation, representing the first demonstration of immune cell-based therapy for OA. Mechanistically, these macrophages orchestrate chondroprotection not through broad immunosuppression, but by activating a TNFAIP3-dependent signaling hub that restrains inflammatory and catabolic responses in chondrocytes. This TNFAIP3 activation precisely reversed the OA-associated gene signature, suppressing catabolic mediators while enhancing reparative factors, thereby restoring the anabolic-catabolic balance. Our findings uncover a developmental blueprint for engineering pro-regenerative macrophages from stem cells and establish a pioneering targeted immune cell therapy that engages an intrinsic chondroprotective program, offering a transformative and translationally relevant strategy for OA treatment.

immunology↗

bioRxiv2025

Neddylation Regulates Mitochondrial Dynamics and Turnover in the Adult Heart

BACKGROUNDDisruption of mitochondrial homeostasis drives cardiomyopathy and heart failure, yet upstream regulatory mechanisms remain poorly defined. Neddylation, a reversible post-translational conjugation of the ubiquitin-like protein NEDD8 by E1/E2/E3 enzymes, is essential for cardiac morphogenesis, but its role in the adult heart is unknown. METHODSWe assessed the relevance of neddylation to human cardiac disease by gene set enrichment analysis of ischemic (ICM) and non-ischemic cardiomyopathy (NICM) datasets and by immunoblotting and qPCR of ventricular tissue from patients with ICM or dilated cardiomyopathy (DCM). In adult mice, we induced cardiomyocyte-restricted deletion of the NEDD8-activating enzyme 1 (NAE1) by tamoxifen injection and monitored cardiac function at baseline and after transverse aortic constriction (TAC). Bulk RNA-seq 4 weeks post-tamoxifen was combined with bioenergetic, biochemical, and ultrastructural analyses. To assess mitochondrial dynamics, we generated NAE1/MFN2 and NAE1/DRP1 double-knockout mice. Cullin activity, mitochondrial ubiquitination, and mitophagy were measured in hearts and cultured cardiomyocytes. RESULTSNeddylation pathways were dysregulated in human ICM and NICM datasets and in failing ICM/DCM myocardium. Cardiomyocyte-specific NAE1 deletion caused systolic dysfunction and heart failure by 10 weeks post-tamoxifen, culminating in premature death and exacerbating TAC-induced pressure-overload heart failure. At 4 weeks, NAE1 loss repressed metabolic and mitochondrial bioenergetic programs, reduced ATP production, and impaired respiration. Electron microscopy revealed elongated mitochondria and accumulated mitophagic vesicles, with dysregulation of DRP1, MFN2, PINK1, LC3-II, and p62. DRP1/NAE1 co-deletion accelerated systolic failure relative to either single knockout, whereas MFN2/NAE1 co-deletion did not alter early disease progression, implicating pathogenic mitochondrial hyperfusion. Genetic NAE1 depletion in vivo and pharmacologic NAE1 inhibition in vitro impaired mitophagic vesicle formation and flux, inactivated cullin scaffold proteins, reduced mitochondrial ubiquitination, and blunted mitophagic clearance. CONCLUSIONSCardiac neddylation preserves adult heart function by coordinating mitochondrial fusion-fission dynamics and sustaining cullin-dependent ubiquitination and turnover of damaged mitochondria. These findings identify neddylation as a key regulator of mitochondrial quality control and link its disruption to human cardiomyopathy. Therapeutically, targeting the neddylation-cullin axis may limit mitochondrial dysfunction, enhance mitophagy, and improve energetic reserve in failing hearts, while neddylation signatures in patient myocardium may help guide stratification and precision therapy for cardiomyopathy. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABS* Demonstrates for the first time that the NEDD8-activating enzyme (NAE1)driven neddylation pathway is indispensable for maintaining mitochondrial quality control in the adult heart. * Links loss of neddylation to mitochondrial hyperfusion, impaired mitophagy, and rapid progression to heart failure. * Reveals that neddylation promotes cullin-RING ligase-mediated ubiquitination of damaged mitochondria, coupling mitochondrial dynamics with turnover. What Are the Clinical Implications?* Restoring or enhancing cardiac neddylation may represent a novel therapeutic avenue for cardiomyopathies characterized by mitochondrial dysfunction. * Pharmacologic agents that bolster DRP1-dependent fission or activate cullin neddylation could potentially normalize mitochondrial dynamics and improve myocardial energetics. * Conversely, systemic neddylation inhibitors now in oncology trials warrant careful cardiac monitoring, as they may precipitate mitochondrial injury and heart failure. * Circulating or tissue markers of neddylation might help stratify patients at heightened risk for mitochondrial-driven cardiac disease and guide precision therapy.

physiology↗

bioRxiv2025

Himito: a Graph-based Toolkit for Mitochondrial Genome Analysis using Long Reads

Understanding the genetic and epigenetic regulation of mitochondrial DNA (mtDNA) is essential for elucidating mechanisms of aging and disease. Long-read sequencing can span the entire mitochondrial genome and directly capture base-modification signals, yet analytical tools for such data remain limited. We developed Himito, a graph-based toolkit for analyzing mitochondrial genome using long reads. Himito filters reads originating from nuclear mitochondrial insertions (NUMTs), constructs a sequence graph to represent mtDNA diversity, assembles primary haplotypes, calls variants, and analyzes 5-methylcytosine (5mC) modifications within a unified framework. Benchmarking on high-quality reference datasets shows Himito achieves superior performance in assembly and variant calling compared with existing tools. Applied to the All of Us (AoU) v8 dataset, Himito identified pathogenic mtDNA variants, revealed population-scale haplogroup diversity, and uncovered age-related genetic and epigenetic patterns. These results demonstrate that long-read sequencing, combined with graph-based analysis, enables integrated characterization of mitochondrial genomic and epigenomic variation. Himito is available at https://github.com/broadinstitute/Himito.

bioinformatics↗

bioRxiv2025

BudFinder: A Masked Auto-Encoder Vision Transformer Framework for Yeast Budding Detection

Yeast replicative lifespan is a crucial part of aging research, yet its quantification remains labor-intensive and time-consuming, particularly when using time-lapse imaging and microfluidics. Manual counting methods for cell division events are prone to bias and inefficiency, while existing automated approaches often require extensive annotated datasets. These limitations hinder the adaptability of such tools across different microfluidic setups. To address these challenges, we propose a versatile image analysis approach that accurately detects yeast cell division events. To reduce the burden of requiring a large cell division annotated dataset, we pretrained a Masked Auto-Encoder on large-scale segmented yeast cell images. This substantially reduced the annotated data needed to train the transformer model for detecting cellular division events. Additionally, the model is trained directly on budding event detection, circumventing reliance on arbitrary heuristics, such as changes in cell area. By leveraging self-supervised pretraining, we reduced the training data requirement to fewer than 50 mother cells ([~]1,000 divisions), representing a >5-fold reduction compared to prior methods while maintaining comparable accuracy. Author SummaryOur work addresses a longstanding challenge in in live-cell time-lapse microscopy analysis, namely, automating cellular division tracking while minimizing the amount of training data required. Traditionally, scientists identify each division event by manually inspecting thousands of time-lapse images, a process that is both tedious and prone to bias. While automated tools exist, they often require large amounts of annotated data to work effectively, limiting their use across different experimental setups. To overcome these barriers, we developed BudFinder, which can recognize and track cell divisions with far less training data. Using yeast replicative aging data as an example, we first trained a model to understand what a yeast cell "looks like", using tens of thousands of segmented yeast cell images entrapped in our custom-built microfluidic device. Then, we taught it to detect budding events directly from time-lapse movies. This approach reduces the need for manual labeling by more than five-fold compared to previous structures in place, while maintaining accuracy comparable to existing methods. By making high-throughput analysis of cellular division more accessible, our work paves the way for faster and more scalable quantification of cellular dynamics.

systems biology↗

bioRxiv2025

Senescent astrocytic deposits drive cognitive decline by disrupting tripartite synapse in the aging brain

Brain aging involves synapse decline, with astrocytes playing a key role in synapse homeostasis. However, the impact of astrocyte senescence on synaptic dysfunction and cognitive decline remains unclear. Here, we identified a hallmark of aging astrocytes--Senescent Astrocytic Deposits (SAD) observed at aged rodents, macaques, and human hippocampal astrocytic processes --that is associated with tripartite synapse dysfunction and memory decline. Laser capture microdissection-coupled mass spectrometry (LCM-MS), spatial transcriptome analysis and 3D electron microscopy revealed that SAD are abnormal protein deposits at the processes of ApoE-high expression astrocyte subtype and associated with dysfunctional tripartite synapses. Using a transgenic mouse (Nrbf2 knockout) with accelerated SAD formation as a tool for genetic manipulation, we clearly demonstrated that age-dependent defect of phagocytosis at maturation stage in astrocytic drives SAD accumulation, synaptic injury and cognitive deficits. Collectively, our findings establish SAD as a mechanistic link between astrocyte senescence and synaptic damage, underscoring the critical role of astrocytic phagocytic function in preserving synaptic homeostasis and cognitive function during aging. Significance StatementThis study reveals that impaired phagocytic maturation in senescent astrocytes leads to formation of SAD and impaired synaptic plasticity, identifying hippocampal astrocyte senescence as a key contributor to age-related cognitive decline.

neuroscience↗

bioRxiv2025

RNA viruses in water shape the viromes of shrimp and fish in aquaculture systems

Aquatic environments host immense RNA viral diversity, yet the extent to which waterborne viruses influence the virome of aquatic animals remains unclear. Here, we conducted a comprehensive longitudinal metatranscriptomic analysis of water, shrimp, and fish across multiple culture stages in aquaculture systems. We identified 3,211 RNA viruses spanning 21 viral supergroups, with 97.4% representing novel species. Water exhibited the greatest viral diversity (3,093 species), followed by shrimp (1,280) and fish (398), with most viruses detected in shrimp and fish also detected in water. Diversity analyses revealed increasing richness and significant compositional shifts in 92 high-abundance viruses (>1,000 RPM) across culture stages. Viral abundance in aquatic animals was strongly correlated with that in water, and the temporal trajectories of the 16 most abundant viruses were closely synchronized between water and shrimp. Furthermore, 337 virus species were shared among shrimp and two fish species, of which 309 were present in water. These findings demonstrated that RNA viruses in water shape the composition and dynamics of aquatic animal viromes, underscoring the importance of water virome surveillance and management for disease prevention in shrimp aquaculture.

microbiology↗

bioRxiv2025

Ethylene receptors are functionally conserved in calcium permeability across the green lineage

The gaseous hormone ethylene plays a key role in regulating plant growth and stress responses. Although Ca{superscript 2} has long been implicated in ethylene signaling, the identity of molecules controlling Ca{superscript 2} permeability involved has remained elusive. Here we show that Arabidopsis ethylene receptors ETR1 and ERS1 are Ca2+ permeable, and that ETR1 mediates ethylene-induced cytosolic Ca2+ increase and regulates hypocotyl elongation. Homologs of ETR1 from eight land plant and algal species also exhibit Ca{superscript 2} permeability, suggesting an evolutionarily conserved function. We further demonstrate ethylene enhances the Ca2+ permeability of ETR1 and its homologue from the charophyte Klebsormidium flaccidum. These findings uncover a previously unrecognized but conserved role of ethylene receptors in Ca{superscript 2} permeability regulation in the green lineage, with broad implications for Ca{superscript 2} signaling in plant development and environmental adaptation.

plant biology↗

bioRxiv2025

FDA-approved drug repurposing in zebrafish identifies thyroid hormone and other compounds as potential antithrombotics

Venous thromboembolism (VTE) is a highly prevalent medical condition with limited therapeutic options and an incomplete understanding of its acquired and inherited subtypes. The zebrafish is a model with the benefits of external development, fecundity, optical transparency, and hemostasis that demonstrates conservation with mammals. We utilized zebrafish as a phenotypic screening tool to identify novel therapeutic options for preventing VTE. A library of FDA-approved compounds was screened for suppression of acquired (elevated estrogen) and spontaneous (protein C deficiency) thrombosis. We found that thyroid hormone, receptor tyrosine kinase (RTK) inhibitors, and proton-pump inhibitors (PPIs) effectively modulated levels of thrombosis, particularly in the estrogen-induced model. These also showed a more favorable hemostatic profile than standard therapies, suggesting alternative mechanisms. Genome editing of thyroid hormone receptor proved that thyroid hormone action is on target. A retrospective electronic health record (EHR) analysis found that thyroid-hormone prescriptions in hormonal contraceptive users correlated with a higher VTE risk, potentially limiting direct repurposing but highlighting thyroid signaling as a pathway involved in estrogen-induced thrombosis. Together, these data identify several drug classes that can be tailored to specific subtypes of VTE and help elucidate distinct pathways driving thrombosis.

pharmacology and toxicology↗

bioRxiv2025

Brain Preparedness for Active Forgetting: Cortisol Awakening Response Proacts Prefrontal Control Over Hippocampal-Striatal Circuitry

Stress-related psychiatric pathologies (e.g., rumination in depression, intrusive memories in PTSD) involve impaired inhibitory control over emotional memories and disrupted cortisol circadian rhythms. However, how these mechanisms interact to support adaptive forgetting remains unclear. Here, by integrating multi-modal neuroendocrine profiling with fMRI-based memory suppression in 90 participants, we demonstrate that the cortisol awakening response (CAR)--a circadian surge priming the brain for daily demands--proactively and selectively enhances suppression of recently acquired but not overnight-consolidated emotional memories. This time-dependent facilitation manifests through dual neural mechanisms: Robust CAR broadly amplifies dorsolateral prefrontal cortex (dlPFC) engagement during suppression attempts and specifically strengthens top-down dlPFC control over hippocampal-striatal circuits exclusively for recent traces. Our findings bridge circadian biology, systems neuroscience, and clinical psychopathology to establish CAR as a neuroendocrine preparedness mechanism that proactively configures adaptive forgetting circuits across sleep-wake cycles, thereby informing circadian-based interventions for stress disorders.

neuroscience↗

bioRxiv2025

TESSA: A unified model to detect trajectory-preserved and spatially-variable genes in spatial transcriptomics

Identifying spatially variable genes (SVGs) has been an essential task in spatial transcriptomics. In addition to SVGs detection, there are genes exhibiting expression patterns that are associated with cellular developmental stages or lineage fates across a tissue section. Identifying such genes could provide novel insights into tumor metastasis. Here, we introduce a unified statistical model, termed TrajEctory-preServed and SpAtially-variable gene detection (TESSA), to detect both types of genes. Moreover, we propose a novel strategy to address the inherent double-dipping issue commonly encountered when assessing temporal gene effects in transcriptomics analysis. We demonstrate the testing performance through extensive simulation studies and real applications to several publicly available datasets. Downstream analyses further highlight the potential of our method in identifying genes associated with tumor progression and enhancing spatial domain detection.

bioinformatics↗

bioRxiv2025

MBOAT7 and CDS2 coordinate lipid droplet dynamics and cholesterol metabolism in liver

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent disorder worldwide characterized by the accumulation of hepatic lipid droplets (LDs). However, the mechanisms by which hepatocytes adapt to the dynamic changes in LD morphology to maintain metabolic homeostasis remains incompletely understood. Here, we show that MBOAT7, a known MASLD-associated protein, cooperates with CDS2 to regulate lipid droplet dynamics and lipid metabolism. Under physiological conditions, their interaction in the endoplasmic reticulum (ER) maintains metabolic homeostasis. Disruption of this interaction, such as through CDS2 knockdown or loss of function, triggers an adaptive response wherein MBOAT7 translocates to ER-LD contact sites in a RAB1-dependent manner. This redistribution inhibits DGAT2-mediated LD growth and promotes lipolysis. Our findings highlight the redistribution of MBOAT7 to ER-LD contacts serves as a critical mechanism for adaptive control LD size and lipid metabolic homeostasis.

cell biology↗

bioRxiv2025

Comparative Temporal Transcriptomic Analysis of SOD1 Mutations in iPSC-Motor Neurons

Mutations in the SOD1 gene are among the most significant genetic contributors to amyotrophic lateral sclerosis (ALS), with different variants linked to varying disease severity. To investigate the molecular mechanisms driving this variability, we conducted RNA sequencing on spinal motor neurons (MNs) differentiated from isogenic human induced pluripotent stem cell (iPSC) lines engineered via CRISPR/Cas9. These lines carried two representative SOD1 heterogenous mutations, D91A and G94A, and were analyzed at Days 10 and 20 of neuronal maturation stage to capture the temporal changes of gene expression. We aim to explore how these mutations affect MN function, identify distinct molecular pathways that may explain the variable severity of ALS, and investigate the role of translation and metabolic dysregulation in disease progression.

bioinformatics↗

bioRxiv2025

AtlasAgent: Vision language model and Agent-guided Framework for Evaluation of Atlas-scale Single-cell Integration

As single-cell omics transitions into the era of AI-virtual cells (AIVC), where large-scale single-cell data integration becomes prevalent, the computational demands of integration evaluation emerge as critical scalability bottlenecks. Traditional integration evaluation pipelines, requiring metrics like k-nearest-neighbor batch effect test (kBET) and Local Inverse Simpsons Index (iLISI) employed by state-of-the-art scIB method, often demand large computational resources and long runtimes, making them infeasible for large scale integration studies. Herein, we present AtlasAgent, the first vision-language model (VLM)-powered and AI agent framework to accelerate atlas-scale integration evaluation at unprecedented speed and scale. We systematically evaluate batch correction quality, biological signal preservation and overcorrection risks using chain-of-thought reasoning in conjunction with few-shot and zero-shot prompting strategies. AtlasAgent completes evaluation within 32 seconds, in contrast to scIBs runtime of 5.55 hours in GPU, while identifying the scIB-determint best integration methods within the top-3 in 88.3% of the time, lowering evaluation time from hours to seconds while preserving alignment with domain expert reasoning. AtlasAgent pioneers the use of VLMs to realize scalable and rapid integration evaluation at atlas scale.

bioinformatics↗

bioRxiv2025

Increased Synapse Elimination by Inflammatory Cells Contributes to Long-lasting Post-Stroke Memory Dysfunction in Old Mice

Old patients are more likely to experience memory dysfunction than young patients after a stroke. It has been reported that brain astrocytes and microglia cause excessive removal of synapses at the acute and subacute stages of stroke, and inhibition of their phagocytosis improved neurobehavioral outcomes. We hypothesized that memory dysfunction in old subjects is associated with increased synapse removal by inflammatory cells. Ischemic stroke was induced in young (2-month-old) and old (15-18-month-old) mice. Memory functions were analyzed by the Y-maze test weekly for 8 weeks and the novel object recognition (NOR) test at 7 days before and 8 weeks post-stroke. We have also created a tibia fracture 6 hours before stroke injury in young mice, to test if the activation of 7-nicotinic acetylcholine receptor (nAchRs) reduces inflammatory cells and synapse elimination. Brains were collected 8 weeks after the induction of ischemic stroke. Transcriptome changes, neuronal injuries, neuroinflammation, synapse removal, and neurite outgrowth were analyzed. We found that old mice developed long-term memory dysfunction after ischemic stroke, which was not seen in young mice. Old mice showed larger infarct volume, higher neuroinflammation, and more synapses engulfed by microglia/macrophages and astrocytes in the peri-atrophic region and hippocampi than young mice. More synapse-engulfing astrocytes than microglia/macrophages were present in the peri-atrophic region and the ipsilateral hippocampi, suggesting that reactive astrocytes contributed more than activated microglia/macrophages in synapse removal. Activation of 7-nAchRs in mice subjected to tibia fracture 6 hours before ischemic injury reduced synapse removal by microglia/macrophages and astrocytes in the hippocampi. Our study indicated that an increase in synaptic elements by inflammatory cells contributes to the long-lasting memory deficit after stroke in old mice. Astrocytes may contribute more than microglia/macrophages in synapse removal. Inhibition of neuroinflammation by activating 7-nAchRs can reduce synapse loss and thus may improve post-stroke memory function.

neuroscience↗

bioRxiv2025

A parallelly distributed microscope and software system for scalable high-throughput multispectral 3D imaging

Recent advances in high throughput optical microscopy have achieved whole-organism scale imaging at diffraction-limited resolutions. Current microscopes, however, require making compromises between achieving the optimal resolution, imaging depth, multispectral capability, and data throughput due to limitations in optical design and data stream handling. We have created a parallel-line scanning confocal microscope (plSCM) which provides 1.1 Gigavoxels/second high speed imaging while achieving an optical resolution of [~]180 x 220 x 650 nm with 2 millimeters of imaging depth in 3 simultaneous spectral channels. To handle such a massive imaging data stream, we have engineered a scalable network-distributed image acquisition/processing framework (SNDiF), which allows continuous capture, real-time processing, and cluster storage of petabyte-scale single image datasets in days. Together, our parallelly distributed microscope and software system presents a general solution for large-scale high-throughput and high-resolution multicolor imaging which can operate for days at a time.

bioengineering↗