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Luo, X.

Publications and source records attributed to Luo, X..

At least 91 records · Page 5Linked to original sources

MARVEL: Microenvironment Annotation by Supervised Graph Contrastive Learning

Recent advancements in in situ molecular profiling technologies, including spatial proteomics and transcriptomics, have enabled detailed characterization of the microenvironment at cellular and subcellular levels. While these techniques provide rich information about individual cells spatial coordinates and expression profiles, extracting biologically meaningful spatial structures from the data remains a significant challenge. Current methodologies often rely on unsupervised clustering followed by cell type annotation based on differentially expressed genes within each cluster and most of the time will require other information as the reference (e.g., HE-stained images). This is labor-intensive and demands extensive domain knowledge. To address these challenges, we propose a supervised graph contrastive learning framework, MARVEL. MARVEL is a supervised graph contrastive learning method that can effectively embed local microenvironments represented by cell neighbor graphs into a continuous representation space, facilitating various downstream microenvironment annotation scenarios. By leveraging partially annotated examples as strong positives, our approach mitigates the common issues of false positives encountered in conventional graph contrastive learning. Using real-world annotated data, we demonstrate that MARVEL outperforms existing methods in three key microenvironment-related tasks: transductive microenvironment annotation, inductive microenvironment querying, and the identification of novel microenvironments across different slices.

bioinformatics↗

CIGB-300 reverses chemo-resistance in MDR1-transfected lung squamous cancer cells

BackgroundInhibition of ABC transporter protein activity is considered to be the most effective method to reverse multidrug resistance (MDR). In this study, we evaluated the MDR reversal potential of CIGB-300, a potent CK2 kinase inhibitor. MethodsABCB1 overexpressing lung adenocarcinoma NCI-H226 cells were constructed using lentivirus, and the expression of ABCB1 gene and protein was detected by real-time fluorescence quantitative PCR and Western blotting. MTT assay was used to assess the cytotoxicity and MDR reversal effect of CIGB-300.The effect of CIGB-300 on ABCB1 expression was determined by Western Blotting. Cell surface expression and subcellular localization of ABCB1 were examined by Flow Cytometry and Immunofluorescence Staining. Rh123 efflux and accumulation were measured by Fluorescent Enzyme Labeler and Flow Cytometry. ResultsCIGB-300 significantly increased the sensitivity of drug-resistant cells overexpressing the ABCB1 drug efflux pump (NCI-H226-ABCB1), while it had no effect on their parental cell lines. At the same time, its mechanism of action may be related to the inhibition of ABCB1 expression, which was dose-dependent, Moreover, in addition, we demonstrated that CIGB-300 reduced the expression of NFKB and CDC37 proteins. ConclusionsOur study elucidated that CIGB-300 reverses ABCB1-mediated MDR by inhibiting ABCB1 protein expression or intracellular signaling and provides a potential therapeutic strategy to improve tumor chemosensitivity.

cancer biology↗

Morphine-induced hyperalgesia impacts small extracellular vesicle miRNA composition and function

Morphine and other synthetic opioids are widely prescribed to treat pain. Prolonged morphine exposure can paradoxically enhance pain sensitivity in humans and nociceptive behavior in rodents. To better understand the molecular mechanisms underlying opioid-induced hyperalgesia, we investigated changes in miRNA composition of small extracellular vesicles (sEVs) from the serum of mice after a morphine treatment paradigm that induces hyperalgesia. We observed significant differential expression of 18 miRNAs in sEVs from morphine-treated mice of both sexes compared to controls. Several of these miRNAs were bioinformatically predicted to regulate cyclic AMP response element binding protein (CREB), a well-characterized transcription factor implicated in pain and drug addiction. We confirmed the binding and repression of Creb mRNA by miR-155 and miR-10a. We tested if serum-derived sEVs from morphine-treated mice could elicit nociceptive behavior in naive recipient mice. Intrathecal injection of 1 g sEVs did not significantly impact basal mechanical and thermal threshold in naive recipient mice. However, prophylactic 1 g sEV administration in recipient mice resulted in faster resolution of complete Freunds adjuvant-induced mechanical and thermal inflammatory hypersensitivity. Other behaviors assayed following administration of these sEVs were not impacted including sEV conditioned place preference and locomotor sensitization. These results indicate that morphine regulation of serum sEV composition can contribute to analgesia and suggest a potential for sEVs to be a non-opioid therapeutic intervention strategy to treat pain.

neuroscience↗

Variations in the temperature dependence of photosynthesis among nine common tree species planted in Singapore

Tree planting is regarded as one of the most cost-effective ways to mitigate climate change impacts. As a part of the global tree planting movement, the tropical city-state of Singapore initiated a project to plant one million trees in 10 years. However, the environmental impacts (e.g., carbon sequestration, urban cooling) of this reforestation effort are challenging to assess as historically we lack understanding of key plant traits (i.e. photosynthetic capacity, or Vcmax) for species in tropical Asia. Here, we conducted a comprehensive survey of key photosynthetic traits of the nine most popular tree species planted in Singapore and their short-term temperature dependence. We found a three-fold inter-species variation in their photosynthetic capacities (e.g., Vcmax ranges from 20 to 60 mol m-2 s-1) as well as a large discrepancy in their temperature dependence. The photosynthesis of some species (e.g., Tembusu) is more sensitive to rising temperature than others (e.g., Mangroves) while a commonly-used photosynthesis model consistently overestimates photosynthesis but underestimates many species temperature sensitivities. The species with smaller temperature sensitivity of photosynthesis is likely related to their stronger ability to adjust leaf temperature via transpiration. Our study provides critical information on the temperature-dependence of photosynthesis of tree species in tropical Asia, which can be used to guide reforestation in Singapore and broadly in Southeast Asia.

plant biology↗

Examining perfluorohexane sulfonate (PFHxS) impacts on sensorimotor and circadian rhythm development

Perfluorohexane sulfonate (PFHxS) is a ubiquitous perfluoroalkyl substance known for its environmental persistence and potential toxicity. This study investigated PFHxSs impact on zebrafish embryos, focusing on sensorimotor behavior, circadian rhythm disruption, and underlying molecular mechanisms. Under 24 hr dark incubations, PFHxS exposure induced concentration-dependent hyperactivity within larval photomotor response, characterized by the distinctive "O-bend" response, strong light-phase hyperactive movement and seizure-like movements. It appears that PFHxS-treated embryos cannot sense light cues in a normal manner. Similar hyperactivity was seen for acoustic startle response assay, suggesting that the response is not merely visual, but sensorimotor. LC-MS studies confirmed detectable uptake of PFHxS into embryos. We then conducted mRNA-sequencing across multiple time points (48 and 120 hpf) and concentrations (0.00025, 0.0025 and 25 {micro}M). Data at the 25 {micro}M (2-120 hpf) exposure showed disrupted pathways associated with DNA and cell cycle. Interestingly, data at 0.00025 {micro}M - an environmentally relevant concentration- at 48 hpf showed disruption of MAPK and other signaling pathways. Immunohistochemistry of eyes showed reduced retinal stem cell proliferation, consistent with observed DNA replication pathway disruptions. To assess if these impacts were driven by circadian rhythm development, we manipulated light/dark cycles during PFHxS incubation; this manipulation altered behavioral patterns, implicating circadian rhythm modulation as a target of PFHxS. Since circadian rhythm is modulated by the pineal gland, we ablated the gland using metronidazole; this ablation partially rescued hyperactivity, indicating the glands role in driving the phenotype. Collectively, these findings underscore proclivity of PFHxS to cause neurodevelopmental toxicity, necessitating further mechanistic exploration and environmental health assessments.

pharmacology and toxicology↗

Foundry-fabricated dual-color nanophotonic neural probes for photostimulation and electrophysiological recording

SignificanceCompact tools capable of delivering multicolor optogenetic stimulation to deep tissue targets with sufficient span, spatiotemporal resolution, and optical power remain challenging to realize. Here, we demonstrate foundry-fabricated nanophotonic neural probes for blue and red photostimulation and electrophysiological recording, which use a combination of spatial multiplexing and on-shank wavelength-demultiplexing to increase the number of on-shank emitters. AimWe demonstrate Si photonic neural probes with 26 photonic channels and 26 recording sites, which were fabricated on 200-mm diameter wafers at a commercial Si photonics foundry. Each photonic channel consists of an on-shank demultiplexer and separate grating coupler emitters for blue and red light, for a total of 52 emitters. ApproachWe evaluate neural probe functionality through bench measurements and in vivo experiments by photostimulating through 16 of the available 26 emitter pairs. ResultsWe report neural probe electrode impedances, optical transmission, and beam profiles. We validated a packaged neural probe in optogenetic experiments with mice sensitive to blue or red photostimulation. ConclusionsOur foundry-fabricated nanophotonic neural probe demonstrates dense dual-color emitter integration on a single shank for targeted photostimulation. Given its two emission wavelengths, high emitter density, and long site span, this probe will facilitate experiments involving bidirectional circuit manipulations across both shallow and deep structures simultaneously.

neuroscience↗

Building a literature knowledge base towards transparent biomedical AI

As artificial intelligence (AI) continues to advance and scale up in biomedical research, concerns about AIs trustworthiness and transparency have grown. There is a critical need to systematically bring accurate and relevant biomedical knowledge into AI applications for transparency and provenance. Knowledge graphs have emerged as a powerful tool that integrates heterogeneous knowledge by explicitly describing biomedical knowledge as entities and relationships between entities. However, PubMed, the largest and most comprehensive repository of biomedical knowledge, exists primarily as unstructured text and is under utilized for advanced machine learning tasks. To address the challenge, we developed LiteralGraph, a computational framework to extract biomedical terms and relationships from PubMed literature into a unified knowledge graph. Using this framework, we established the Genomic Literature Knowledge Base (GLKB), which consolidates 14,634,427 biomedical relationships between 3,276,336 biomedical terms from over 33 million PubMed abstracts and nine well-established biomedical repositories. The database is coupled with RESTful APIs and a user-friendly web interface that makes it accessible to researchers for various usages. We demonstrated the broad utility of GLKB towards transparent AI in three distinct application scenarios. In the LLM grounding scenario, we developed a Retrieval Augmented Generation (RAG) agent to reduce LLM hallucination in biomedical question answering. In the hypothesis generation scenario, we elucidated the potential functions of RFX6 in type 2 diabetes (T2D) using the vast evidence from PubMed articles. In the machine learning scenario, we utilized GLKB to provide semantic knowledge in predictive tasks and scientific fact-checking.

bioinformatics↗

Identification and Diagnostic Potential of Pyroptosis-Related Genes in Endometriosis: A Novel Bioinformatics Analysis

ObjectiveThis study aimed to identify and analyze potential signatures of pyroptosis-related genes in EMs. MethodsTranscriptomic datasets related to endometriosis were retrieved from the GEO databases (GSE7305, GSE7307, and GSE11691). Differential gene expression analysis was performed to identify pyroptosis-related differentially expressed genes (PRDEGs) by intersecting DEGs with a curated list of PRGs. Various bioinformatics tools were employed to explore the biological functions and pathways associated with PRDEGs. ResultsWe identified 26 PRDEGs from combined datasets and constructed an EMs diagnostic model using LASSO regression based on pyroptosis scores. The model included 5 DEGs: KIF13B, BAG6, MYO5A, HEATR, and AK055981. Additionally, 21 Key Module Genes (KMGs) were identified, leading to the classification of 3 distinct EMs subtypes. These subtypes were analyzed for immune cell infiltration, revealing a complex immune landscape in EMs. ConclusionsThis study reveals pyroptosis crucial role in EMs and offers a novel diagnostic model based on pyroptosis-related genes. Modulating pyroptosis may provide a new therapeutic approach for managing EMs.

bioinformatics↗

Vapor pressure deficit dominates the spatiotemporal variations in ecosystem photosynthetic quantum yield

O_LIThe quantum yield () of photosynthesis represents the maximum efficiency of light use as indicated by the initial slope of photosynthetic light response curves. Understanding is crucial for accurate modeling of photosynthesis and terrestrial carbon cycle. Despite its importance, the spatial and temporal variations in at large scales remain largely elusive. C_LIO_LIWe leveraged long-term eddy-covariance observations from 90 sites globally and examined the spatiotemporal variations in due to climatic drivers, using statistical and machine learning approaches. C_LIO_LIWe found significant spatial variability in across and within biomes, primarily driven by atmospheric vapor pressure deficit and soil moisture variations. Meanwhile, the temporal changes in are mainly driven by the negative effect of vapor pressure deficit, which weakens the positive effects of elevated CO2 and leaf area index. C_LIO_LIOur results highlight the dominant role of vapor pressure deficit in controlling the spatiotemporal variations of as well as the unneglectable impacts of soil water content, CO2, and leaf area on . Those new results provide insights for improving the representation of in ecosystem photosynthesis models. C_LI

ecology↗

Benchmarking Recent Computational Tools for DNA-binding Protein Identification

Identification of DNA-binding proteins (DBPs) is a crucial task in genome annotation, as it aids in understanding gene regulation, DNA replication, transcriptional control and various cellular processes. In this paper, we conduct an unbiased benchmarking of eleven state-of-the-art computational tools as well as traditional tools such as ScanProsite, BLAST, and HMMER for identifying DBPs. We highlight the data leakage issue in conventional datasets leading to inflated performance. We introduce new evaluation datasets to support further development. Through a comprehensive evaluation pipeline, we identify potential limitations in models, feature extraction techniques and training methods; and recommend solutions regarding these issues. We show that combining the predictions of the two best computational tools with BLAST based prediction significantly enhances DBP identification capability. We provide this consensus method as user-friendly software. The datasets and software are available at: https://github.com/Rafeed-bot/DNA_BP_Benchmarking. 1. Key PointsO_LIWe designed a comprehensive evaluation pipeline which systematically evaluates eleven recent machine learning (ML) based DBP identification tools. C_LIO_LIWe analyzed the test prediction mistakes made by top-performing tools identifying their potential limitations in terms of model architecture, feature extraction and class balancing. C_LIO_LIWe showed that although the best of these tools do not convincingly outperform BLAST, they still provide substantial value when integrated together with BLAST into a simple majority-voting ensemble. C_LIO_LIWe provide recommendations on more robust development & evaluation and better usability of future tools. C_LIO_LIWe provide the two best-performing ML-based tools, BLAST and the ensemble method as user-friendly software, as well as our proposed datasets, publicly available via GitHub. C_LI

bioinformatics↗

VISTA Uncovers Missing Gene Expression and Spatial-induced Information for Spatial Transcriptomic Data Analysis

Characterizing cell activities within a spatially resolved context is essential to enhance our understanding of spatially-induced cellular states and features. While single-cell RNA-seq (scRNA-seq) offers comprehensive profiling of cells within a tissue, it fails to capture spatial context. Conversely, subcellular spatial transcriptomics (SST) technologies provide high-resolution spatial profiles of gene expression, yet their utility is constrained by the limited number of genes they can simultaneously profile. To address this limitation, we introduce VISTA, a novel approach designed to predict the expression levels of unobserved genes specifically tailored for SST data. VISTA jointly models scRNA-seq data and SST data based on variational inference and geometric deep learning, and incorporates uncertainty quantification. Using four SST datasets, we demonstrate VISTAs superior performance in imputation and in analyzing large-scale SST datasets with satisfactory time efficiency and memory consumption. The imputation of VISTA enables a multitude of downstream applications, including the detection of new spatially variable genes, the discovery of novel ligand-receptor interactions, the inference of spatial RNA velocity, the generation for spatial transcriptomics with in-silico perturbation, and an improved decomposition of spatial and intrinsic variations.

bioinformatics↗

Microbial Weathering Analysis of Anshun Tunbao Artifacts

AbstractsCultural heritages are the crystallization of human technology, culture and embody the efforts of many craftsmen in ancient times. Wooden cultural heritages are affected by their own materials, and are very susceptible to microbial invasion under suitable temperature and humidity conditions. This project mainly studies the microbial weathering of the core wood carving masks and wooden ancient stage in Anshun Tunpu cultural heritage, and uses scanning electron microscopy, high-throughput sequencing and traditional culture methods to analyze the characteristics of their microbial communities, and finds that the bacteria represented by Pseudomonas, Paenibacillus and Stenotrophomonas, and the fungi represented by Cladosporium, Alternaria and Aspergillus, are the core microorganisms shared by indoor and outdoor cultural heritage. The dominant genera such as Pseudomonas, Stenotrophomonas, and Cladosporium showed lignocellulose deradation ability. By cultivating insect eggs extracted from sampled specimens and analyzing the correlation with surface microbiota, we verified the role of insect eggs as vectors in dispersing key microbial communities. We speculate that these insects are likely to be Anobiidae family. Furthermore, by comparing the microbial compositions under different climatic conditions, we validated the influence of temperature, humidity, vegetation diversity, and microbial intrinsic structures on microbial growth. Therefore, monitoring the surrounding environment is crucial in microbial weathering studies and cultural heritage preservation efforts. This study pioneered the investigation of microbial weathering aspects on unique heritage of the Tuenbao culture, emphasizing the importance of preserving distinctive ethnic cultures. Additionally, it presented a case study on the microbial weathering of wooden artifacts in karst landscape environments.

microbiology↗

Long-Range Enhancer Networks Gradually Emerge as Key Regulators During Human Cortical Neurogenesis

The chromatin in the human brain cortex shows more enhancer-enhancer contacts than in macaques and mice, yet the organization of these contacts across cellular states and their mechanisms remain unclear. Here, we developed SCOPE-C, a cost-effective technique designed for mapping DNase I Hypersensitive Sites and their spatial interactions, with the potential for scalability to single-cell resolution. Employing SCOPE-C, we generated a comprehensive chromatin map detailing cis-regulatory elements in four cell types during neurogenesis in human, macaque, and mouse fetal cortex. This map introduces a model of long-range enhancer networks that regulate gene transcription during human cortical neurogenesis. In this model, CTCF-mediated loop extrusion forms stripes of enhancer interaction hubs extending up to 10 Mb in human Excitatory Neurons. Enriched with human-specific enhancers and neuropsychiatric disorder-linked SNPs, these remarkably long-range networks predominantly control EN marker genes, suggesting their critical role in robust gene expression during human cortical neurogenesis.

genomics↗

The cGAS-STING Pathway Is Essential in Acute Ischemia-Induced Neutropoiesis and Neutrophil Priming in the Bone Marrow

Acute myocardial ischemia triggers a rapid mobilization of neutrophils from the bone marrow to peripheral blood, facilitating their infiltration into the infarcted myocardium. These cells are critical for inducing inflammation and contributing to myocardial repair. While neutrophils in infarcted tissue are better characterized, our understanding of whether and how ischemia regulates neutrophil production, differentiation, and functionality in the bone marrow remains limited. This study investigates these processes and the influence of the cGAS-STING pathway in the context of myocardial infarction. The cGAS-STING pathway detects aberrant DNA within cells, activates STING, and initiates downstream signaling cascades involving NFKB and IRF3. We analyzed neutrophils from bone marrow, peripheral blood, and infarct tissues using MI models generated from wild-type, Cgas-/-, and Sting-/- mice. These models are essential for studying neutropoiesis (neutrophil production and differentiation), as it involves multiple cell types. RNA sequencing analysis revealed that ischemia not only increased neutrophil production but also promoted cytokine signaling, phagocytosis, chemotaxis, and degranulation in the bone marrow before their release into the peripheral blood. Inhibition of the cGAS-STING pathway decreased neutrophil production after MI and down-regulated the same pathways activated by ischemia. Neutrophils lacking cGAS or STING were less mature, exhibited reduced activation, and decreased degranulation. Deletion of cGAS and STING decreased the expression of a large group of IFN-stimulated genes and IFIT1+ neutrophils from peripheral blood and the infarct tissue, suggesting that cGAS-STING plays an essential role in neutrophils with the IFN-stimulated gene signature. Importantly, transcriptomic analysis of Cgas-/- and Sting-/- neutrophils from bone marrow and MI tissues showed downregulation of similar pathways, indicating that the functionality developed in the bone marrow was maintained despite infarct-induced stimulation. These findings highlight the importance of neutropoiesis in dictating neutrophil function in target tissues, underscoring the critical role of the cGAS-STING pathway in neutrophil-mediated myocardial repair post-ischemia.

immunology↗

Phase transition of WTAP regulates m6A modification of interferon-stimulated genes

N6-methyladenosine (m6A) is the most prevalent modification of mRNA which controls diverse physiological processes. Although m6A modification has been reported to regulate type I interferon (IFN) responses by targeting the mRNA of IFN-{beta} and the interferon stimulated genes (ISGs), the detailed mechanism of how m6A methyltransferase complex (MTC) rapidly responds to conduct the modification on nascent mRNA during IFN-{beta} stimulation remains largely unclear. Here, we demonstrate that WTAP, the adaptor protein of m6A MTC, undergoes dephosphorylation-regulated phase transition from aggregates to liquid-like condensates under IFN-{beta} stimulation, thereby mediates m6A modification of a subset of ISG mRNAs to restrict their expression. The phase transition of WTAP promotes the interaction with nucleus-translocated transcription factor STAT1, which recruits MTC to the promoter regions of ISGs and directing the co-transcriptional m6A modification on ISG mRNAs. Collectively, our findings reveal a novel regulatory role of WTAP phase transition in manipulating signaling pathways and fine-tuning immune response by orchestrating dynamic m6A modification through the cooperation of transcription factors and MTC.

immunology↗

YTHDF2 upregulation and relocation dictate CD8 T cell polyfunctionality in tumor immunity

Epigenetic traits impact the antitumor function of CD8 T cells, yet whether and how RNA methylation programs engage in T cell immunity is poorly understood. Here we show that the N6-methyladenosine (m6A) RNA reader YTHDF2 is highly expressed in early effector or effector-like CD8 T cells and is partially distributed in the nucleus. YTHDF2 loss in T cells exacerbates tumor progression and confers unresponsiveness to PD-1 blockade in mice and humans. In addition to initiating RNA decay for mitochondrial fitness, YTHDF2 can orchestrate chromatin regulation to promote T cell polyfunctionality. YTHDF2-mediatd preservation of gene transcription arises from the interaction of YTHDF2 with IKZF1/3. Accordingly, immunotherapy-induced efficacy could be largely restored in YTHDF2-deficient T cells through combinational use of lenalidomide. Moreover, m6A recognition is fundamental for YTHDF2 translocation to the nucleus and autoregulation at the RNA level. Thus, YTHDF2 coordinates epitranscriptional and transcriptional networks to potentiate T cell immunity. HighlightsO_LIYTHDF2 expression and distribution underpin the threshold for bona fide CD8 T cell effector response C_LIO_LICanonical YTHDF2-mRNA decay pathway alleviates mitochondrial stress and CD8 T cell exhaustion C_LIO_LINuclear YTHDF2 sequesters IKZF1/3-mediated transcriptional repression to safeguard CD8 T cell polyfunctionality C_LIO_LIThe tumoricidal activity of YTHDF2-deficient CD8 T cells could be repaired through the synergy of anti-PD-1 and lenalidomide C_LI

immunology↗

Repeat and haplotype aware error correction in nanopore sequencing reads with DeChat

Error self-correction is a pivotal first step in the analysis of long-read sequencing data. However, most existing methods for this purpose are primarily tailored for noisy sequencing data with error rates exceeding 5%, often collapsing true variants in repeats and haplotypes. Alternatively, some methods are heavily optimized for PacBio HiFi reads, leaving a gap in methods specifically designed for Nanopore R10 reads basecalled with high accuracy or super accuracy models, which typically have error rates below 2%. Here, we introduce DeChat, a novel approach specifically designed for Nanopore R10 reads. DeChat enables repeat- and haplotype-aware error correction, leveraging the strengths of both de Bruijn graphs and variant-aware multiple sequence alignment to create a synergistic approach. This approach avoids read overcorrection, ensuring that variants in repeats and haplotypes are preserved while sequencing errors are accurately corrected. Benchmarking experiments reveal that reads corrected using DeChat exhibit substantially fewer errors, ranging from several times to two orders of magnitude lower, compared to the current state-of-the-art approaches. Furthermore, the application of DeChat for error correction significantly improves genome assembly across various aspects. DeChat is implemented as a highly efficient, standalone, and user-friendly software and is publicly available at https://github.com/LuoGroup2023/DeChat.

bioinformatics↗

Defining the cellular origin of seminoma by transcriptional and epigenetic mapping to the normal human germline

Aberrant male germline development can lead to the formation of seminoma, a testicular germ cell tumor. Seminomas are biologically similar to primordial germ cells (PGCs) and many bear an isochromosome 12p [i(12p)] with two additional copies of the short arm of chromosome 12. By mapping seminoma transcriptomes and open chromatin landscape onto a normal human male germline trajectory, we find that seminoma resembles premigratory/migratory primordial germ cells, but exhibit enhanced germline and pluripotency programs, and upregulation of genes involved in apoptosis, angiogenesis, and MAPK/ERK pathways. Using pluripotent stem cell-derived PGCs from Pallister Killian syndrome patients mosaic for i(12p) to model seminoma, we identify gene dosage effects that may contribute to transformation. As murine seminoma models do not exist, our analyses provide critical insights into genetic, cellular and signaling programs driving seminoma transformation, and the newly developed in vitro platform permits evaluation of additional signals required for seminoma tumorigenesis.

developmental biology↗