Biology subjects

Yue, X.

Publications and source records attributed to Yue, X..

At least 19 recordsLinked to original sources

bioRxiv2026

Porcine epidemic diarrhea virus Whole-Genome Diversity Reveals Divergence of Contemporary Populations in the United States

Porcine epidemic diarrhea virus (PEDV) was introduced into the United States (USA) in 2013 and has circulated ever since. PEDV causes significant losses in the swine industry, with the greatest impact observed during the first years following its introduction into the country. However, the evolutionary dynamics of the virus remain underexplored. Recently, analyses of the Spike protein subunit S1 suggested that the PEDV population currently circulating in the USA represents a fraction of its historical diversity and comprises only two clades restricted to specific geographic regions. These observations were based on a limited set of S1 sequences. Furthermore, our understanding of evolutionary dynamics at the genomic level is even more limited, as complete PEDV genomes have not been generated since 2017. Here, we characterized the evolutionary dynamics of PEDV populations in the USA using complete genomes and assessed the contribution of different evolutionary mechanisms to shaping population structure. We analyzed 338 complete genomes, of which 25 were obtained in this study, together with 623 Spike S1 sequences, of which 41 were obtained in this study. All sequences obtained in this study were assigned to the non-S-INDEL strain. No S-INDEL sequences were recovered in this study, although these viruses continue to circulate in the country. Our analyses revealed that most sequences sampled after 2023 formed a monophyletic clade divergent from sequences collected in previous years, suggesting an ongoing temporal population structuring. Population structure analyses further supported evidence of population differentiation over time. Recombination analyses indicated that sequences belonging to the contemporary clade shared a single recombination event, suggesting that this clade may have emerged through recombination. Time-scaled S1 phylogenies were consistent with previous findings, supporting the circulation of only two contemporary clades; however, one of these clades was detected for the first time outside its previously reported geographic range. Our findings document temporal genetic differentiation in US PEDV populations, consistent with continued viral evolution, and broaden the known geographic distribution of contemporary S1 clades. These results highlight the value of continued genomic surveillance to monitor changes in PEDV diversity and distribution and provide sequence data to inform vaccine research.

microbiology↗

bioRxiv2026

A PVH-to-parabrachial BDNF circuit mediates non-aversive feeding suppression

Parabrachial nucleus (PBN) CGRP neurons mediate aversive feeding suppression, but PBN circuitry governing homeostatic, non-aversive feeding suppression remains poorly understood. Here, we identify a circuit in which paraventricular hypothalamus (PVH) neurons innervate BDNF-expressing ventrolateral/dorsolateral PBN (vl/dlPBNBDNF) neurons, which project to multiple hypothalamic nuclei. Refeeding strengthens excitatory and weakens inhibitory synaptic transmission in LPBN-projecting PVH neurons and preferentially induced Bdnf and Fos in vl/dlPBNBDNF neurons compared with elPBNCGRP neurons, whereas noxious LPS preferentially activated elPBNCGRP neurons. Gain- and loss-of-function experiments demonstrated that vl/dlPBNBDNF neurons are sufficient and necessary for feeding suppression without inducing conditioned taste aversion and that this effect require BDNF-TrkB signaling. In addition to hypothalamic inputs, vl/dlPBNBDNF neurons receive dense inputs from major downstream targets of elPBNCGRP neurons. Thus, vl/dlPBNBDNF neurons define a non-aversive feeding-suppression circuit positioned to integrate hypothalamic homeostatic signals with aversive signals, thereby coordinating food intake with internal energy needs and potentially harmful physiological conditions.

neuroscience↗

bioRxiv2026

USP20 Stabilizes FABP5 to Drive Macrophage Foam Cell Formation and Atherosclerosis

Background: Macrophage foam cell formation is a central event in atherosclerosis. Although protein ubiquitination is increasingly recognized as a regulator of macrophage lipid handling, whether deubiquitinating enzymes directly control lipid uptake and metabolic remodeling during atherogenesis remains unclear. Methods and Results: Here, transcriptomic profiling identified ubiquitin-specific protease 20 (USP20) as a previously unrecognized regulator of macrophage foam cell formation. Genetic and pharmacological studies demonstrated that USP20 promoted macrophage lipid accumulation and foam cell formation, whereas macrophage-specific Usp20 deficiency markedly attenuated atherosclerotic lesion formation, lipid deposition, and macrophage accumulation in mice. To elucidate the underlying mechanism, integrative analysis of USP20-interacting proteins and proteomic alterations in Usp20-deficient macrophages identified fatty acid-binding protein 5 (FABP5) as a substrate of USP20. Mechanistically, USP20 interacted with FABP5 and stabilized its protein abundance by preventing ubiquitin-dependent proteasomal degradation. Consequently, USP20-mediated stabilization of FABP5 enhanced PPAR{gamma} occupancy at the Cd36 promoter, thereby increasing Cd36 transcription, ox-LDL uptake, and foam cell formation. Accordingly, Fabp5 knockdown abolished USP20-induced CD36 expression, ox-LDL uptake, and foam cell formation, whereas pharmacological activation of PPAR{gamma} restored CD36 expression in Fabp5-deficient macrophages. Finally, macrophage-targeted delivery of the USP20 inhibitor GSK2643943A markedly reduced atherosclerotic burden without evident systemic toxicity, supporting the therapeutic potential of targeting USP20 in atherosclerosis. Conclusions: USP20 promotes macrophage foam cell formation by stabilizing FABP5 and enhancing PPAR{gamma}-dependent Cd36 transcription. Targeting the USP20-FABP5-PPAR{gamma}-CD36 axis may represent a therapeutic strategy to limit macrophage lipid accumulation, metabolic dysfunction, and atherosclerosis progression.

cell biology↗

bioRxiv2026

Transcription factors read a second regulatory code in chromatin

Transcription factors (TFs) decode gene regulatory information written in DNA, yet how this vocabulary is interpreted within chromatin remains largely unexplored. Here, using an upgraded NCAP-SELEX platform, we systematically map the nucleosomal DNA recognition landscapes of 269 human TFs. We uncover a widespread, chromatin-dependent mode of sequence recognition: many TFs recognize motifs on nucleosomal DNA that are distinct from their canonical naked-DNA binding sites, revealing that nucleosome architecture encodes a second gene regulatory code in chromatin. Cryo-electron microscopy structures of TF-nucleosome complexes demonstrate that this second code is read through a combination of nucleosome-induced DNA deformation and direct protein-histone contacts. Functional analyses show that these chromatin-encoded motifs actively promote chromatin accessibility and drive cell-type-specific cis-regulatory activity in vivo. Strikingly, a single TF can deploy its canonical and nucleosome-derived motif repertoires to partition and govern entirely distinct physiological programs. Together, our findings establish that TFs interpret two complementary layers of genomic information: the primary DNA sequence and a second code written into the nucleosome architecture. This chromatin-encoded layer of regulatory information fundamentally expands our understanding of how TF specificity is achieved and how gene regulatory networks are wired in multicellular organisms.

systems biology↗

bioRxiv2026

An EEG-fMRI Jointly Constrained Digital Twin Brain and Its Application in Alzheime's Disease

Current digital twin brain (DTB) models are typically optimized using single-modality functional neuroimaging data, which restricts their ability to simulate brain dynamics across multiple spatiotemporal scales. Here, we bridged this gap by developing a two-stage DTB (TS-DTB) modeling framework jointly constrained by functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) data. Validation in both the healthy young and Alzheimers disease (AD) cohorts demonstrated that the TS-DTB model simultaneously captures subject-specific features of multi-scale brain dynamics. In particular, the TS-DTB models of AD patients successfully recapitulated spectral-temporal signatures of cognitive decline, mechanistically linking these deficits to excitation-inhibition (E-I) imbalances. By simulating responses to repetitive transcranial magnetic stimulation (rTMS), we further revealed that cognitive recovery in AD patients can be driven by E-I rebalancing via synaptic reconfiguration and background suppression. Overall, these findings underscore the potential of the TS-DTB to advance the mechanistic understanding of the brain and inform personalized digital therapeutics.

neuroscience↗

bioRxiv2025

Crosstalk between the Methyl-Cytosine Dioxygenase TET3 and the Methyl-CpG-binding protein MECP2 Controls Neuronal Maturation

Active DNA demethylation depends on Ten-Eleven-Translocation (TET) enzymes, which oxidize 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC) and further derivatives. Mutations in TET3, encoding the predominant neuronal isoform, lead to Beck-Fahrner syndrome, a neurodevelopmental disorder. Using human iPSC-derived neurons, we show that TET3 is dispensable for neuronal specification but critical for subsequent maturation. Differentiating TET3-deficient neurons exhibit delayed transcriptional and proteomic transitions, altered synaptic signatures, and impaired network activity, indicating delayed functional maturation. Mechanistically, we identified an interaction between TET3 and the mC/hmC-binding protein MECP2, pathogenic variants of which cause Rett syndrome. MECP2 negatively regulates TET3 activity, as demonstrated in functional assays and by inverse hmC patterns in MECP2- and TET3-deficient neurons. Despite this, MECP2- and TET3-deficient neurons exhibit highly similar phenotypes later in differentiation. Our findings uncover a functional interplay between TET3 and MECP2 that coordinates DNA methylation and chromatin dynamics during neuronal maturation, suggesting a shared pathogenic mechanism in Beck-Fahrner and Rett syndromes.

neuroscience↗

bioRxiv2025

IS110 transposon utilizes two mechanistically distinct RNA-guided transposition pathways

The recently discovered IS110 elements employ RNA-guided transposases that use bridge-RNA to coordinate donor and target DNA recognition and integration via donor- and target-binding loops, offering promise for precise, DSB-free genome editing. However, their transposition mechanism remains unclear, with prior inconsistent observations. Using a IS110 element from Caloranaerobacter azorensis, we show that IS110 transposons utilize two independent transposition pathways. The first depends on bridge-RNA and excises the element via copy-out to form a circular intermediate, revisiting the earlier cut-out model. Integration occurs predominantly through top-strand insertion, suggesting an alternative to the earlier Holliday junction-mediated dual-strand mechanism. The second involves cooperation between a truncated target-binding loop RNA and bridge-RNA, enabling direct top-strand transfer to a new target via two sequential reactions, bypassing circular intermediates. Both pathways preserve the original transposon copy. These findings redefine the mechanistic understanding of IS110 transposition and reconcile prior discrepancies, offering insight into programmable, RNA-guided genome modification.

molecular biology↗

bioRxiv2025

The Cumulative Distribution Function Based Method for Random Drift Model

We propose a numerical method to uniformly handle the random genetic drift model for pure drift with or without natural selection and mutation. For pure drift and natural selection case, the Dirac {delta} singularity will develop at two boundary ends and the mass lumped at the two ends stands for the fixation probability. For the one-way mutation case, known as Mullers ratchet, the accumulation of deleterious mutations leads to the loss of the fittest gene, the Dirac {delta} singularity will spike only at one boundary end, which stands for the fixation of the deleterious gene and loss of the fittest one. For two-way mutation case, the singularity with negative power law may emerge near boundary points. We first rewrite the original model on the probability density function (PDF) to one with respect to the cumulative distribution function (CDF). Dirac {delta} singularity of the PDF becomes the discontinuity of the CDF. Then we establish a revised finite difference method(rFDM), which keeps the total probability, is positivity-preserving and unconditionally stable. For pure drift, the scheme also keeps the conservation of expectation. It can catch the discontinuous jump of the CDF, then predicts accurately the fixation probability for pure drift with or without natural selection and one-way mutation. For two-way mutation case, it can catch the power law of the singularity. The numerical results show the effectiveness of the scheme. We also compare rFDM with a standard finite difference method(sFDM). We find that, for pure drift problem, sFDM fails to keeps the conservation of expectation and can not predict the fixation probability, because there is artificial mutation introduced near two boundary ends.

genetics↗

bioRxiv2025

Modeling neurodegenerative diseases in Drosophila is conditioned by stress resistance and gut microbiome composition of the reference line

Drosophila is widely used to study the pathological mechanisms of human diseases in vivo, including metabolic and neurological disorders. In these models, disease-induced alterations in locomotion and stress resistance are generally monitored in comparison to healthy control flies, such the white-eyed strain w1118, used as a reference for normal physiology and behavior. Here we compared two independent w1118 lines and found that they differed strikingly in their susceptibility to oxidative stress and nutrient starvation, and less markedly in their locomotor performance. Interestingly, modulating the gut microbiome by rearing these flies under axenic conditions increased oxidative stress resistance of the more susceptible, but not the more resistant line, while it had no effect on starvation resistance for both lines. We also found that the stress-sensitive line had higher levels of Clostridiales bacteria and of the intracellular endosymbiont Wolbachia in the gut microbiota, as well as lower expression levels of immune effectors (antimicrobial peptides and lysozymes) in the head and gut. Both lines nevertheless showed similar susceptibility to pathogenic bacterial infections. In a transgenic Parkinsons disease model, the stress-resistant background strongly attenuated the progressive locomotor defects induced by pan-neuronal expression of human mutant -synuclein, but intriguingly not when -synuclein expression was restricted to a subset of brain dopaminergic neurons in the protocerebral anterior medial (PAM) cluster. These results suggest that taking into account unapparent features of the reference lines could improve the reproducibility and consistency of neurodegenerative disease models in Drosophila.

neuroscience↗

bioRxiv2025

In vivo Calcium Imaging in the Near-Infrared II Window

Non-invasive deep-tissue calcium imaging of live mammals with high sensitivity and resolution is challenging owing to light scattering experienced by traditional calcium ion (Ca2+) indicators with excitation and emission wavelengths within 400-750 nm. Here, we report near-infrared II (NIR-II) calcium imaging beyond 1000 nm by exploring a natural protein derived from a bacterium (Thermochromatium tepidum) living in a calcium carbonate-rich environment. This highly photostable fluorescent protein enables NIR-II imaging of intracellular Ca2+ responses to stimulant drugs in cultured mammalian cells with sensitivity comparable to that of visible Ca2+ indicators. We achieve in vivo NIR-II imaging of Ca2+ transients in response to two different tumor treatment strategies in intact tumors with high sensitivity, resolution, and contrast, opening the possibility of non-invasive deep-tissue calcium imaging for assessing treatment efficacy longitudinally. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/661443v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@149504eorg.highwire.dtl.DTLVardef@37722borg.highwire.dtl.DTLVardef@2878a7org.highwire.dtl.DTLVardef@1091d0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Resistance to heavy metals and genome sequencing of ESBL-producing and non-ESBL-producing Escherichia coli

The present study aimed to examine the impact of heavy metals on the resistance levels exhibited by ESBL-producing and non-ESBL-producing Escherichia coli. The minimum inhibitory concentration (MIC) of six heavy metals on two types of E. coli was determined using the broth microdilution method. Heavy metal resistance genes were detected via PCR amplification, and the gene structures were analyzed through whole genome sequencing. The findings indicated that ESBL-producing E. coli strains exhibited significantly higher levels of resistance to Cu, Zn, and Cd compared to non-ESBL-producing strains. Additionally, ESBL-producing strains harbored various plasmid-mediated heavy metal resistance genes. The results of WGS demonstrated that ESBL-producing strains carried plasmids encoding 148 heavy metal resistance genes, and the resistance to certain antibiotics (e.g., chloramphenicol) in E. coli exhibited a significantly negative correlation with resistance to specific heavy metals, including Mn and Cd (p < 0.05). The present study hypothesizes the presence of synergistic mechanisms between heavy metal resistance and antibiotic resistance in ESBL-producing E. coli, including the dual functionality of the efflux pumping system, the synergistic regulation of the pressure response system, and the physical barrier effect of biofilm formation. The experimental findings revealed the link between heavy metals and antibiotic resistance, highlighting the importance of environmental monitoring and control of heavy metal pollution. Further studies are warranted to explore the mechanisms by which heavy metals promote the transfer of genes associated with antibiotic resistance in order to formulate effective intervention strategies to combat this issue.

microbiology↗

bioRxiv2025

Functional Characterization of Paillotin: An Immune Peptide Regulated by the Imd Pathway with Pathogen-Specific Roles in Drosophila Immunity

Insects, such as Drosophila melanogaster, rely on innate immune defenses to combat microbial threats. Antimicrobial peptides (AMPs) play an important role in limiting pathogen entry and colonization. Despite intensive research into the regulation and biochemical properties of AMPs, their exact significance in vivo has remained uncertain due to the challenges of mutating small genes. Fortunately, recent technologies have enabled the mutation of individual AMP genes, overcome previous obstacles, and opened new avenues for research. In this study, we characterized one novel host-defense peptide, Paillotin (IM18, CG33706), using loss-of-function mutants. Paillotin is an ancient host defense peptide of Diptera, regulated by the Imd pathway. Loss of Paillotin does not impact the activity of either the Imd or Toll pathways. Importantly, we found that Paillotin mutants are viable but exhibit increased susceptibility to specific infections, particularly Providencia burhodogranariea. Paillotin was further found to contribute synergistically to defense against P. burhodogranariea when combined with other AMPs. However, we did not detect direct microbicidal activity of Paillotin in vitro in our hands. Taken together, our findings identify Paillotin as a novel host defense peptide acting downstream of Imd signaling, advancing our understanding of the Drosophila antimicrobial response.

immunology↗

bioRxiv2025

Hippocampal single-cell RNA Atlas of chronic methamphetamine abuse-induced cognitive decline in mice

BackgroundChronic methamphetamine abuse leads to cognitive decline, posing a significant threat to human health and contributing to loss of productivity. However, the intricate and multifaceted mechanisms underlying methamphetamine-induced neurotoxicity have impeded the development of effective therapeutic interventions. MethodsTo establish a mouse model of cognitive decline induced by chronic methamphetamine exposure, we employed a large sample size and conducted two behavioral tests (Y-maze and novel object recognition test) at 2 and 4 weeks post-exposure. Subsequently, single-cell RNA sequencing was utilized to delineate the mRNA expression profiles of individual cells within the hippocampus. Comprehensive bioinformatics analyses, including cell clustering and identification, differential gene expression analysis, cellular communication analysis, pseudotemporal trajectory analysis, and transcription factor regulation analysis, were performed to elucidate the cellular-level changes in mRNA profiles caused by chronic methamphetamine exposure. ResultsOur findings demonstrated impairments in working memory, spatial cognition, learning, and cognitive memory. After 4 weeks of behavioral testing, we identified diverse cell types in the hippocampi of METH- and saline-treated mice through scRNA-seq, including glial cells, stromal cells, vascular cells, and immune cells. We observed that methamphetamine exerts cell-specific effects on gene expression changes associated with neuroinflammation, blood-brain barrier disruption, neuronal support dysfunction, and immune dysregulation. Furthermore, cross-talk analysis revealed extensive alterations in cellular communication patterns and signal changes within the hippocampal microenvironment induced by methamphetamine exposure. Pseudotime analysis predicted hippocampal neurogenesis disorders and identified key regulatory genes implicated in chronic methamphetamine abuse. Transcription factor analysis uncovered regulators and pathways linked to astrocyte-mediated neuroinflammation, endothelial junction integrity, microglial synaptic remodeling, and oligodendrocyte-supported neuronal cell bodies and axons. Additionally, it highlighted the role of neural precursor cells in various forms of neurodegeneration. ConclusionsThis study establishes a robust mouse model of cognitive impairment induced by chronic methamphetamine exposure. It provides valuable biological insights, characterizes the single-cell atlas of the hippocampus, and offers novel directions for investigating neurological damage associated with chronic methamphetamine-induced cognitive decline.

pharmacology and toxicology↗

bioRxiv2024

Non-Invasive dsRNA Delivery via Feeding for Effective Gene Silencing in Teleost Fish: A Novel Approach in the Study of Gene Function Analysis

RNA interference is a powerful technique for gene silencing, involving post-transcriptional regulation of gene expression. Successful application of RNAi has been demonstrated in various organisms like nematodes, insects, and oysters by ingesting dsRNA-expressing bacteria. In this study, we attempted a non-invasive feeding method in the marine economy teleost fish, Sebastes schlegelii. To validate the feasibility of this approach in S. schlegelii, we utilized rotifers (Brachionus plicatilis), Artemia nauplii, and commercial pellet feed as vectors to deliver Escherichia coli strain HT115 engineered to express double-stranded RNA (dsRNA), targeting dead end (dnd) gene, known to be important for primordial germ cells (PGCs) migration and proliferation in fish. Our experimental results consistently showed that knockdown of the dnd gene effectively inhibited the development of PGCs in S. schlegelii, resulting in gonadal dysplasia and even sex reversal. This study marks a significant advancement in understanding gene function in teleost fish, laying the groundwork for future large-scale research in this field.

genetics↗

bioRxiv2024

OGT prevents DNA demethylation and suppresses the expression of transposable elements in heterochromatin by restraining TET activity genome-wide

The O-GlcNAc transferase OGT interacts robustly with all three mammalian TET methylcytosine dioxygenases. We show here that deletion of the Ogt gene in mouse embryonic stem cells (mESC) results in a widespread increase in the TET product 5-hydroxymethylcytosine (5hmC) in both euchromatic and heterochromatic compartments, with concomitant reduction of the TET substrate 5-methylcytosine (5mC) at the same genomic regions. mESC engineered to abolish the TET1-OGT interaction likewise displayed a genome-wide decrease of 5mC. DNA hypomethylation in OGT-deficient cells was accompanied by de-repression of transposable elements (TEs) predominantly located in heterochromatin, and this increase in TE expression was sometimes accompanied by increased cis-expression of genes and exons located 3 of the expressed TE. Thus, the TET-OGT interaction prevents DNA demethylation and TE expression in heterochromatin by restraining TET activity genome-wide. We suggest that OGT protects the genome against DNA hypomethylation and impaired heterochromatin integrity, preventing the aberrant increase in TE expression observed in cancer, autoimmune-inflammatory diseases, cellular senescence and ageing.

molecular biology↗

bioRxiv2023

DNA sensor ABCF1 phase separates with cccDNA to inhibit HBV replication

Objectives: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) contributes to viral persistence and recurrence. However, it is still less known how the host immune system responds to cccDNA and suppresses HBV replication. Therefore, it is essential to explore host proteins that interact with cccDNA and efficiently suppress HBV replication. Design: The interaction of cccDNA and ABCF1 was assessed by ChIP and pull-down assay. HBV replication was assessed in different cell models, including cccDNA surrogate-transfected and HBV-infected hepatocytes models. Phase separation of recombinant ABCF1 fusion proteins with cccDNA was observed by fluorescence microscopy. Results: Our data found that ABCF1 interacts with cccDNA to form phase-separated condensates via the poly-glutamine (PolyQ) of N-terminal intrinsically disordered low-complexity domain (LCD). Subsequently, ABCF1-cccDNA phase separation not only activates the type I/III interferon (IFN-I/III) pathway but also prevents Pol II accumulation on cccDNA to inhibit HBV transcription. Conclusions: Taken together, our study showed that ABCF1 acts as an antiviral restriction factor of HBV cccDNA by phase-separation-driven innate immune signaling and transcription inhibition. These findings shed new light on the understanding of host defense against cccDNA and provide a novel promising therapeutic strategy for HBV infection.

microbiology↗

bioRxiv2023

Ciliary ARL13B prevents obesity in mice

Primary cilia are sensory cellular appendages that regulate diverse developmental and homeostatic processes, including energy homeostasis. In animal models and humans, their dysfunction can lead to hyperphagia and obesity. ARL13B is a regulatory GTPase enriched in cilia. We engineered an Arl13b mouse allele, Arl13bV358A, that disrupts ARL13B from localizing to primary cilia. Homozygous Arl13bV358A/V358A mice become hyperphagic, obese, and insulin resistant. Restoring wildtype ARL13B to cilia in 4-week-old Arl13bV358A/V358A mice fully rescued the obesity and metabolic dysfunction. Additionally, the selective exclusion of ARL13B from cilia in the nervous system caused obesity. Together, these findings establish that ciliary ARL13B function within the nervous system is necessary for body weight regulation. Our ability to genetically uncouple the ciliary and non-ciliary functions of ARL13B in a cell-type-specific manner enables us to define its cilia-specific role and offers new insights into the molecular mechanisms underlying primary cilia control of energy homeostasis.

genetics↗

bioRxiv2023

Patient-derived organoids assist personalized treatment for a patient with multiple metastatic neuroendocrine carcinoma of the cervix

Neuroendocrine carcinoma of the cervix (NECC) is a rare subtype of cervical cancer with rapid metastasis. Lack of treatment regimens for metastatic NECC highlights the need for preclinical models and personalized treatment. Here, we established two patient-derived NECC organoid lines from lung metastases from the same patient, one of which was drug-free and the other exhibited tolerance to carboplatin plus etoposide (EP). The two organoids recapitulated the histopathology and genomic spectrum of the original tumors. Whole-genome sequencing revealed genomic structural variations (SVs), including HPV16 infection, NEUROD2, and ERBB2 amplification. The sensitivity phenotype of organoids to ERBB2 inhibitors coincides with the genomic features of ERBB2 amplification. In addition, the patient after relapse responded well to the paclitaxel plus carboplatin (TC) regimen as recommended by organoid drug screening, underscoring the utility of organoids as preclinical models. We first provide two NECC organoids of lung metastases with comprehensive molecular characteristics as valuable resources for this rare cancer and give a typical application for personalized treatment based on organoids.

cancer biology↗