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Biology subjects

Sun, Z.

Publications and source records attributed to Sun, Z..

At least 73 records · Page 4Linked to original sources
bioRxiv2025

A stress-dependent TRIM28-ALKBH2 feedback loop modulates chemotherapy response

Chemoresistance to DNA-damaging agents, including platinum and alkylating compounds, limits treatment efficacy in non-small cell lung cancer (NSCLC) and is frequently associated with elevated DNA repair activity. Here, we identify a stress-responsive feedback loop between the E3 ligase TRIM28 and the demethylase ALKBH2. TRIM28 binds ALKBH2 and promotes its K48-linked polyubiquitination and proteasomal degradation, whereas ALKBH2 enhances TRIM28 transcription and protein levels, forming a feedback loop. Notably, alkylation stress induces a biphasic response: acute MMS exposure enhances TRIM28-ALKBH2 association and accelerates ALKBH2 degradation, whereas prolonged exposure promotes TRIM28 degradation, leading to ALKBH2 stabilization and transcriptional upregulation. Clinically, ALKBH2 is frequently elevated in lung adenocarcinoma and is associated with worse survival, whereas TRIM28 exhibits prognostic value specifically in chemotherapy-treated patients. Functionally, MMS-cisplatin co-treatment increased DNA damage and reduced clonogenic survival by counteracting ALKBH2-dependent alkylation tolerance, linking the TRIM28-ALKBH2 loop to chemoresistance in NSCLC.

biochemistry↗
bioRxiv2025

Sensory neuronal mTORC1 signaling establishes neuroimmune memory that initiates allergic immunity

Environmental allergens are enriched in protease activity, a feature that directly activates cutaneous sensory neurons, triggering itch and Substance P release, which promotes Th2-skewing CD301b+ dendritic cell migration and initiates allergic immunity. However, allergens are typically encountered as repeated, subthreshold exposures, and how these cumulatively induce sensitization is unknown. We identify a sensory neuron-intrinsic mechanism of neuroimmune memory that enables this process. Initial activation by protease allergens induces sustained mTORC1 signaling and PGC-1-associated mitochondrial remodeling, establishing a metabolically primed state that amplifies neuroimmune responses upon allergen re-exposure. This heightened state, independent of adaptive immunity, drives enhanced itch, increased CD301b+ dendritic cell migration, and augmented Th2 differentiation. Disrupting neuronal mTORC1 signaling or mitochondrial stability abrogates this amplification while leaving primary responses intact. Importantly, this mechanism generalizes across distinct protease allergens, revealing mTORC1-driven metabolic reprogramming in sensory neurons as a form of innate neuroimmune memory underlying allergen cross-sensitization and polysensitization.

immunology↗
bioRxiv2025

The assembly of stress granule-like foci during foot-and-mouth disease virus infection is uncoupled from activation of cellular intrinsic antiviral signalling

Foot-and-mouth disease virus (FMDV) is highly contagious among cloven-hoofed animals and poses a major threat to the livestock industry worldwide. A fundamental gap in knowledge for high consequence viruses such as FMDV is understanding how the virus evolved to evade cellular antiviral responses. FMDV belongs to the Picornaviridae, a family of positive-sense single-stranded RNA viruses. The detection of viral double-stranded viral RNA intermediates during infection can trigger both the assembly of cytoplasmic stress granules (SGs) and the activation of the RIG-I-like receptors (RLR)-mediated innate immune response (IIR). FMDV has been proposed to antagonize these mechanisms, suggesting that both can limit viral replication. In this study, we investigate the dynamic and importance of SG assembly for IIR activation upon dsRNA stimulation or FMDV replication in porcine epithelial kidney cells. First, we show that the formation of SG following a challenge with poly(I:C), a viral dsRNA mimic, does not modulate the activation of IIR. Our data further reveal transient assembly of SG during FMDV infection followed by virus-induced cleavage of G3BP1, a core SG protein. While SG assembly does not impact viral replication or antiviral response activation, we demonstrate that preventing their disassembly negatively impacts FMDV replication. Overall, our data suggests that while SGs assembly is uncoupled from IIR activation, manipulating their disassembly limits replication and might serve as a potential therapeutic target to prevent FMDV infection. ImportanceBiomolecular condensates, including stress granules, are key regulatory compartments that control fundamental cellular processes. By condensing RNAs and proteins, these structures enable cells to rapidly adapt to stress, such as viral infection. Different biomolecular condensates with specific dynamics or compositions have been described during infection, and many viruses are known to disrupt or highjack their components. Moreover, the cell-autonomous innate immune response is proposed to be regulated by biomolecular condensates. However, the molecular mechanisms underpinning these functions remain unclear and controversial. Here we investigated the interplay between stress granules and the innate response upon the stimulation with a viral dsRNA mimic or foot-and-mouth disease virus infection. We demonstrate that infection triggers the formation of stress granules independently from activation of innate signalling pathways. We also show that stress granules persistence attenuates viral replication posing them as part of the cells response that viruses must overcome or subvert to replicate.

microbiology↗
bioRxiv2025

A cortical signature of very preterm birth across development and its association with neurodevelopmental outcomes

Gestational age plays a crucial role in neurodevelopment, and individuals born very preterm (VPT; <32 weeks gestation) are at elevated risk for cognitive, behavioural and psychiatric problems across the lifespan. Better understanding of the impact of very preterm birth on cortical maturation trajectories could inform mechanistic insights into the origins of these sequelae. Here we compared cortical morphology between VPT individuals and full-term controls in three datasets spanning birth, childhood and adulthood. We identified a consistent cortical signature of VPT birth, characterized by reduced surface area and cortical folding in the frontal, temporal, parietal and insular regions, which persisted across development. Furthermore, in two large infant cohorts, we found that this cortical signature was significantly associated with neonatal clinical factors and with poorer motor outcomes at follow-up, suggesting its potential as a neuroimaging marker for long-term neurodevelopmental risk. Given that early motor development plays a key role in shaping infants interactions with the environment and supporting later cognitive and behavioural development, our findings provide insights into the neurobiological pathways linking VPT birth to subsequent neurodevelopmental difficulties.

neuroscience↗
bioRxiv2025

Single-cell transcriptomic profiling of bam mutant tumor reveals germline heterogeneity and gcrf1 as a modulator in Drosophila germ cells

The bam mutant ovary of Drosophila represents a classic tumor model caused by germline stem cell (GSC) differentiation defects. To date, its molecular and genetic features have rarely been characterized in detail at the single-cell resolution. Here, we performed single-cell RNA sequencing (scRNA-seq) to comprehensively delineate the transcriptomic landscape and identify distinct germline cell types in bam mutant ovaries by using in situ hybridization. Differentially expressed gene analysis and PAGA plots reveal different transcriptional profiles and developmental relationships in ovarian cells. Based on the expression pattern of eggpl, a useful marker for undifferentiated germ cell identity, and morphological differences in bam mutant ovarioles, two potentially distinct germ cell states are distinguished. Comparative single-cell analysis reveals the potential regulatory network and cellular communication in subclusters of undifferentiated germ cells, and contributes to the identification of gcrf1 as a novel marker gene for female GSC, which involves in the regulation of early germ cell proliferation and Drosophila fertility. Collectively, our study not only provides insights into tumorigenesis caused by GSC differentiation defects but also offers a valuable transcriptomic resource that can be mined for the reproductive features of bam mutant tumors by community.

developmental biology↗
bioRxiv2025

ceQTL: A co-expression QTL model to detect a variant that affects transcription factor binding and its target regulation

Expression quantitative trait locus (eQTL) mapping is used to identify a functional link between a genomic variant, such as single nucleotide polymorphism (SNP), and gene expression (often close-by pair for cis-eQTL) by linear regression, commonly done when matching genotype and expression data from same individuals are available. Millions of significant eQTLs have been reported by both individual studies and coordinated large consortiums such as Genotype-Tissue Expression project (GTEx). A significant eQTL association does not establish a causal relationship or provide any underlying mechanism so further investigation is needed to understand how a SNP impacts gene expression. One of the plausible explanations for eQTL is that a genomic variant affects transcription factor (TF) binding and thus impacts its regulation on its target genes (TGs). However, data-driven or formal statistical methods to prove that hypothesis are still lacking. To address the gap, we propose a new method called differential co-expression QTL (ceQTL) among different alleles using Chow statistics to specifically detect eQTLs that are modulated by a particular TF. We start with building a trio of TF, its TG, and related SNP and then test the significant coefficient difference among different levels of SNP in terms of TF and TG correlation. We applied this ceQTL model to simulated data and the lung tissue datasets from the GTEx project. The simulated data results showed that the model was robust to detect true ceQTLs at variable sample sizes and different minor allele frequencies as measured by Area Under the Curve (AUC). In normal lung tissue, a small fraction of eQTLs were found to have strong ceQTLs, i.e., eQTLs where SNP affects gene expression though TF binding. Some ceQTLs may not be detected by traditional eQTL analysis. Our tool also performed a TF binding affinity analysis to add another layer of evidence for functional interpretation. Comparisons with other similar tools were also presented. In summary, ceQTL analysis provides a more interpretable and biological insight into the mechanism of eQTL, which would help us better understand how genomic variants affect phenotypes and diseases.

bioinformatics↗
bioRxiv2025

Crosstalk between Immune Microenvironment and Hair Follicle Cells Underlies Sexual Dimorphism in Androgenetic Alopecia

Androgenetic alopecia (AGA), also known as female pattern hair loss (FPHL) in women, is the most prevalent form of hair loss. It is characterized by progressive miniaturization of hair follicles and shortening of the anagen phase. The condition is widely attributed to genetic predisposition and androgen-mediated activation of androgen receptors. Other factors, such as the immune microenvironment, could also contribute to the pathogenesis. However, the specific mechanisms involved are still poorly understood. This study aimed to investigate the potential role of skin-resident myeloid cells in interacting with hair follicle cells under androgen stimulation, and to elucidate the sex-specific differences in dihydrotestosterone (DHT)-induced hair loss. Both female and male mice received DHT treatment, and histological examination was performed to assess DHT-induced alterations in skin morphology. Single-cell RNA sequencing (scRNA-seq) was utilized to profile skin cell populations and explore underlying mechanisms. Our results demonstrated that DHT inhibited hair regrowth in both sexes, altered skin thickness, and induced hair follicle miniaturization. scRNA-seq analysis revealed enhanced interactions between myeloid and fibroblast subpopulations, with more robust crosstalk observed in female mice. An in vitro experiment demonstrated that DHT promoted apoptosis of dermal papilla cells (DPCs) in the presence of macrophages. Treatment with polypeptides Y001 and Y002 effectively promoted hair regrowth by suppressing apoptosis signaling pathways. Our findings underscore the interactions between immune cells and hair follicular cells, particularly mediated by skin-resident myeloid cells, in the sexual dimorphism of androgenetic alopecia. The polypeptides Y001 and Y002 exhibit promising therapeutic potential by targeting apoptotic pathways, offering novel avenues for AGA treatment.

cell biology↗
bioRxiv2025

A stromatoporoid-like sediment-agglutinating sponge from microbialites of Cambrian Stage 4

Many extant demosponges, especially the non-spicular taxa, incorporate foreign detritus in their spongin or chitinous skeletons. This supposed energy-efficient way of skeleton construction is, however, rarely known in the fossil record. In this study, based on careful petrographic analyses using standard optical microscopy, cathodoluminescence and fluorescence microscopy, and a three-dimensional reconstruction, a fossil from the Cambrian Stage 4 of Xuzhou City, Jiangsu Province, China, is established as a sediment-agglutinating sponge Psammolectospongia beiwangensis gen. et sp. nov. These fossils encrust stromatolitic microbialites and are often surrounded by Girvanella mats. This succession of microbialites and sponge fossils was developed in a turbulent hydrodynamic condition after the deposition of edgewise conglomerates. P. beiwangensis possesses labyrinthine skeletons with an architecture similar to that of some stromatoporoids, such as Stromatopora and Syringostromella, although dissepiments are absent in the Cambrian fossil. The skeleton of P. beiwangensis is mainly composed of packed silt-to sand-sized detritus grains and skeletal fragments of other animals, while in some places, it can contain various proportions of micrites. The morphology and skeletal composition of P. beiwangensis indicate an affinity to an agglutinating demosponge, which mainly constructed its skeleton using agglutinated and incorporated sediments, while the spongin skeleton was able to be biomineralized like that of Vaceletia. This study is the first report of a sponge fossil that mainly built its skeleton using foreign detritus, and it expands our knowledge about the physiology and ecological behaviors of early Paleozoic demosponges.

paleontology↗
bioRxiv2025

Synthesis and In Vitro Characterization of OGA-2506 as a High Affinity Radioligand for O-GlcNAcase

O-GlcNAcase (OGA) is a glycoside hydrolase that regulates protein O-GlcNAcylation, a dynamic post-translational modification implicated in numerous cellular processes. Dysregulation of OGA alters cellular O-GlcNAc homeostasis and has been linked to neurodegenerative and other chronic diseases. The development of radioligands targeting OGA, particularly those derived from well-characterized tool compounds, could substantially advance drug discovery in this area. Herein, we report the radiosynthesis of a novel tritium (3H)-labeled radioligand 7 (code name [3H]OGA-2506) derived from a chiral piperidine scaffold, and its preliminary in vitro binding evaluation. Starting from iodine precursor 8, palladium-catalyzed tritiation afforded [3H]7 with excellent molar activity (1822 GBq/mmol) and high radiochemical purity (>99%). Saturation binding studies revealed that [3H]7 binds OGA with high affinity to rat striatum homogenates (Kd = 3.56 nM; Bmax = 42.62 nM). Competition assays yielded an IC50 of 5.55 nM, and preliminary autoradiography demonstrated heterogeneous regional distribution in the brain with specific binding. These findings highlight [3H]7 as a valuable tool for OGA binding studies and provide a foundation for the future development of novel positron emission tomography (PET) ligands to probe O-GlcNAc signaling in the brain.

pharmacology and toxicology↗
bioRxiv2025

The E. coli PeptideAtlas Build: Characterizing the observed Escherichia coli pan-proteome and its post-translational modifications

Escherichia coli is a widely used model organism in molecular biology. Despite its pivotal role, a comprehensive proteome resource covering the E. coli pan-proteome and its post-translational modifications (PTMs) has been lacking. Here we present the E. coli PeptideAtlas build, the first comprehensive pan-proteome analysis of E. coli, generated from 40 high-quality public and in-house datasets spanning a broad diversity of strains, sample types, and experimental conditions, and comprising over 73 million MS/MS spectra. All datasets were reprocessed using both a closed search (Trans-Proteomic Pipeline using MSFragger) and an open search (ionbot). The E. coli PeptideAtlas build provides evidence for 4,755 proteins, including 1,410 previously lacking protein-level support in UniProt. The resource offers protein coverage, modification sites, raw spectra with matched peptides, and manually annotated metadata for the E. coli pan proteome. PTM profiling identified over 10,000 modification sites, including phosphorylation (3,806), acetylation (754), methylation (730), glutathionylation (352) and phosphoribosylation (226). Analysis of the glutathionylation sites revealed potential links to metal binding regulation. We also detected proteins likely associated with phages, underscoring the value of pan-proteomic approaches for studying host-phage interactions. All identifications are publicly accessible and traceable through the PeptideAtlas interface. We expect that the E. coli PeptideAtlas build will provide a useful resource for the community, which supports, for example, targeted MS experiment design, PTM enrichment method development, and strain typing. It allows straightforward lookups of protein and peptide identifications and facilitates comparative proteomic analyses by enabling the assessment of protein presence and variability across different E. coli strains. The build is available at https://db.systemsbiology.net/sbeams/cgi/PeptideAtlas/buildDetails?atlas_build_id=585.

bioinformatics↗
bioRxiv2025

Changes in sea ice alter genetic structure of an iconic Arctic apex predator in less than three decades

Climate change is having profound effects on biodiversity and species distributions worldwide. Nowhere are these effects potentially more pronounced than in the Arctic, where warming is almost two times the global average, and where year-round sea ice extent has significantly decreased, affecting many ice-dependent species. The polar bear (Ursus maritimus) is a circumpolar, apex Arctic predator, a sentinel of climate change, and a symbol of conservation. It is of immense cultural and spiritual importance to Inuit peoples and is hunted across the Arctic. Declines in sea ice have caused habitat fragmentation and loss, disrupting movement and prey access, potentially altering genetic structure and influencing polar bears potential to persist. Using samples collected from 1997 to 2020 by Inuit across much of the Canadian Arctic, 322 genome-wide autosomal DNA markers specifically designed to quantify polar bear genetic structure and a very stringent spatial-temporal method, we compare polar bear spatial genetic structure and landscape features between two periods across a consistent distribution:1997-2008 and 2009-2020. We observe marked changes in spatial genetic structure across the Arctic Archipelago over just two decades, shifting the boundaries between polar bear genetic clusters by [~]250 km. Landscape resistance models reveal the importance of sea ice and land cover type for each period, with spatial lag models showing that genetic change is best predicted by sea ice shifts between periods. Our study reveals rapid changes in genetic structure of polar bears in the Canadian Arctic, helps to inform conservation and management, and offers insight on future polar bear persistence across its immense, remote distribution.

genomics↗
bioRxiv2025

Clock Modulation by Naringenin via RORα Suppresses Lipogenesis and Promotes Adipose Tissue Browning

The circadian clock orchestrates adipocyte development and lipid remodeling, with its disruption leading to the development of obesity and insulin resistance. Here we demonstrate that the flavonoid compound naringenin displays clock modulatory activity via ROR that suppresses adipocyte lipid storage while promoting browning. In adipogenic progenitors, naringenin activates ROR with induction of clock gene expression to promote circadian clock oscillation with protective effect against cytokine-induced dampening. The clock-enhancing properties of naringenin suppressed lipogenesis in mature adipocytes together with induction of browning characteristics. The inhibitory effect of naringenin on lipogenesis was dependent on clock modulation as it was abolished in ROR-deficient adipocytes. We further show that naringenin administration in vivo up-regulated ROR expression with clock gene induction together with browning of subcutaneous beige fat depot, resulting reduced fat mass and body weight. Naringenin treatment in vivo also lowered plasma glucose and free fatty acid levels, with markedly enhanced insulin signaling in adipose depots and skeletal muscle. Collectively, our findings uncover a new clock-activating mechanism of action in mediating the metabolic benefits of naringenin, suggesting its potential as a natural supplement for anti-obesity and metabolic disease interventions.

cell biology↗
bioRxiv2025

Defined human tri-lineage brain microtissues

Microglia are the immune cells of the central nervous system and are thought to be key players in both physiological and disease conditions. Several microglial features are poorly conserved between mice and human, such as the function of the neurodegeneration-associated immune receptor Trem2. Induced pluripotent stem cell (iPSC)-derived microglia offer a powerful opportunity to generate and study human microglia. However, human iPSC-derived microglia often exhibit activated phenotypes in vitro, and assessing their impact on other brain cell types remains challenging due to limitations in current co-culture systems. Here, we developed fully defined brain microtissues, composed of human iPSC-derived neurons, astrocytes, and microglia, co-cultured in 2D or 3D formats. Our microtissues are stable and self-sufficient over time, requiring no exogenous cytokines or growth factors. All three cell types exhibit morphologies characteristic of their in vivo environment and show functional properties. Co-cultured microglia develop more homeostatic phenotypes compared to microglia exposed to exogenous cytokines. Hence, these tri-cultures provide a unique approach to investigate cell-cell interactions between brain cell types. We found that astrocytes and not neurons are sufficient for microglial survival and maturation, and that astrocyte-derived M-CSF is essential for microglial survival. Single-cell and single-nucleus RNA sequencing analyses nominated a network of reciprocal communication between cell types. Brain microtissues faithfully recapitulated pathogenic -synuclein seeding and aggregation, suggesting their usefulness as human cell models to study not only normal but also pathological cell biological processes.

neuroscience↗
bioRxiv2025

Putative long-range mossy fiber sprouting and regional hypermetabolic capacity in the hippocampus of patients with mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (MTLE) is pathologically characterized by neuronal loss in the dentate hilus, CA3 and CA1 regions, and mossy fiber (MF) sprouting into the inner molecular layer (iML). The latter forms aberrant excitatory circuities that are considered to facilitate recurrent seizures, with the subiculum also being related to epileptogenic activation. We recently identified a distinct expression of -smooth muscle actin (SMA) at the MF terminals in human hippocampus. This prompted us to explore MF sprouting in resected hippocampi (n=20) from patients with MTLE relative to postmortem control (n=20) using SMA along with reference markers for pathological cross-validation. Compared to control, neuronal loss assessed with neuron-specific nuclear antigen and sortilin immunolabeling reached CA1 in all resected hippocampi. SMA, zinc transporter 3 and {beta}-secretase 1 immunolabeling in the iML tended to be increased. The MF-related markers also revealed a preserved fibrous band extending across CA1 to subiculum. Cytochrome c oxidase immunolabeling also increased in iML and subiculum in the MTLE group. Taking together, the current findings point to the existence of long-range MF sprouting and a regional hypermetabolic compacity in the hippocampal formation of patients with drug resistant MTLE.

neuroscience↗
bioRxiv2025

A T-cell Intrinsic Role for APOL1 Risk Alleles in Allograft Rejection

African Americans have an increased risk of kidney disease due to exonic variants in Apolipoprotein-L1 (G1 and G2). These prevalent variants have also been linked with kidney rejection, but outside of association with African ancestry, underpinning causal mechanisms are unknown. We investigated T-cell function using transgenic mice with physiologic expression of wild type (G0-), G1-, or G2-APOL1. Mice with variant APOL1 showed greater CD8+T-cell activation with expansion of a central memory (TCM) subset. Stimulated G1-CD8+T-cells showed enhanced proliferation and cytokine production, which reversed with APOL1 inhibition. In MHC-mismatched cardiac transplants, G1-mice demonstrated greater CD8+T-cell infiltration and reduced survival. Bulk transcriptome of G1-CD8+T-cells, and single-cell transcriptome of graft infiltrating TCMs, showed enrichment of canonical T-cell receptor (TCR) pathways including Ca2+-signaling. G1-CD8+T-cells demonstrated baseline ER-Ca2+ depletion followed by sustained increases in cytosolic-Ca2+ upon TCR stimulation. G1-CD8+T-cells were more sensitive to Ca2+ chelation, or store-operated Ca2+ entry inhibition, and relatively resistant to calcineurin antagonism vs. G0-CD8+T-cells. Analogously, in a kidney transplant cohort, APOL1-variant recipients developed rejection when they had elevated peripheral TCMs before transplantation and despite significantly higher tacrolimus levels vs G0/G0-AAs with rejection. In summary, we unravel an excitatory T-cell intrinsic mechanism for APOL1 exonic variants, causally linking them with kidney rejection.

immunology↗
bioRxiv2025

The human transcription factor occupancy landscape viewed using high-resolution in situ base-conversion strand-specific single-molecule chromatin accessibility mapping

Chromatin accessibility profiling is a key tool for mapping the location of cis-regulatory elements (cREs) in the genome and tracking chromatin state dynamics during development, in response to various external and internal stimuli, and in disease contexts. Single-molecule footprinting (SMF) methods that rely on the labeling of individual accessible DNA bases have emerged in recent years as a powerful chromatin accessibility mapping approach, as they provide not just an average readout of accessibility over a given genomic position but also the distribution of accessibility states within a population at the level of individual original DNA molecules. However, methylation-based SMF approaches have often been limited either in their resolution or in labeling readout accuracy. We developed a deaminase-based high-resolution strand-specific single molecule footprinting approach that uses highly active sequence context-independent endogenous methylation-insensitive double-strand DNA (dsDNA) deaminases (CseDa01 and LbDa02 C[->]U/T-ssSMF), which convert accessible cytosines into uracils (which are converted to thymine after PCR amplification). We demonstrate the application of the method to mapping single-molecule accessibility states in human cell lines in both a short and a long-read format, and quantifying the occupancy states of individual transcription factors (TFs) as well as TF co-accessibility and strand-specific accessibility patterns.

genomics↗
bioRxiv2025

PB-scope: Contrastive learning of dynamic processing body formation reveals undefined mechanisms of approved compounds

Membraneless organelles (MLOs) formed by liquid-liquid phase separation contribute to intracellular compartmentalization of specific biological functions. The dynamic regulation of MLOs is critical for RNA metabolism, stress response, and signal transduction. While the number and size of MLOs serve as valuable indicators of cellular states, leveraging their spatial distribution and diverse quantitative characteristics to infer cellular conditions has posed significant challenges. Here, we present processing body (PB)-scope: an unsupervised deep learning-based framework designed for imaging-based phenotypic screening of PB, one representative MLO. The model was trained on a substantial dataset comprising over 400,000 single-cell confocal microscopy images from a colon cancer cell line treated with 280 compounds. PB-scope enabled precise drug classification based on their effects on PB characteristics, including number and size. This artificial intelligence framework offers insights previously obscured by the dynamic and subtle nature of PBs. Notably, PB-scope identified drugs with a shared function in the JAK signaling pathway, a previously unrecognized regulator of PB dynamics. PB-scope holds the potential for adapting to the study of other MLOs, offering broad applicability in this emerging field of cell biology.

cell biology↗