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Decoding T cell state-specific regulomes in cancer

细胞研究（英文版） 2024年第6期34卷 399-400页

作者： Giulia Escobar Ana C.Anderson Cellular Immunotherapy Program Cancer CenterMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA Cancer Center Massachusetts General HospitalHarvard Medical SchoolBostonMAUSA Ann Romney Center for Neurologic Diseases Harvard Medical School and Brigham and Women's HospitalBostonMAUSA The Gene Lay Institute of Immunology and Inflammation BostonMAUSA

Tumor-infiltrating CD8 T cells comprise a spectrum of differentiation states associated with distinct functional,transcriptional,and epigenetic features;understanding the gene networks regulating each state holds the potential to redirect CD8 T cell functionality towards therapeutically relevant *** a recent Nature paper,Zhou et *** a single-cell CRISPR knock-out screen of 180 transcription factors in tumor-infiltrating CD8 T cells,identify-ing factors that regulate cell state transitions and represent therapeutically actionable targets.

关键词： cancer cell decoding regulomes state-specific

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Attenuation of arsenic-induced gut injury in mice by sulfated glycosaminoglycan from swim bladder via regulation of gut microbiota， metabolites， and intestinal barrier integrity

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Food Science and Human Wellness 2024年

作者： Jieying Ou Xiaofei Liu Jing Chen Houpei Huang Xuejing Jia Baojun Xu Zhiling Yu Saiyi Zhong Shenzhen Research Institute， Guangdong Ocean University Food Science and Technology Program， Department of Life Sciences， BNU-HKBU United International College Centre for Cancer and Inflammation Research， School of Chinese Medicine， Hong Kong Baptist University College of Food Science and Technology， Guangdong Ocean University， Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety

Arsenic， a known environmental carcinogen， disrupts intestinal homeostasis， posing a significant threat to human health. Mitigating its toxic effects is crucial， and this study explores the potential of swim bladder sulfated glycosaminoglycan (SBSG) in achieving this. Our previous in vitro studies have shown SBSG to ameliorate arsenic-induced damage in intestinal epithelial cells， but its in vivo effects remain elusive. The current investigation demonstrates that SBSG exhibits a beneficial prebiotic action in vivo， regulating gut microbiota， metabolites， and intestinal barrier function to counter arsenic's adverse effects. Specifically， SBSG regulates microbiota composition， suppressing pathogenic species like Alistipes and Candidatus＿Saccharimonas while promoting beneficial ones such as Ruminococcus and Akkermansia. In the colon， SBSG fermentation enhances the production of short-chain fatty acids (SCFAs)， leading to upregulation of GPR43， GPR109A， and Olfr78 receptors. Additionally， SBSG strengthens the intestinal barrier by increasing the expression of Claudin-1， Occludin， and ZO-1， and enhances mucin gene expression (MUC-1 and MUC-2) to address chemical barrier disruptions. Immunologically， SBSG modulates the RORγt/Foxp-3 pathway and the TLR4/MyD88/NF-κB signaling cascade， regulating the immune barrier. These findings suggest that SBSG could be a promising prebiotic candidate for maintaining intestinal health and may serve as a dietary supplement or adjunct in heavy metal detoxification therapies.

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Supplying the trip to antibody production-nutrients,signaling,and the programming of cellular metabolism in the mature B lineage

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Cellular & Molecular Immunology 2022年第3期19卷 352-369页

作者： Mark R.Boothby Shawna K.Brookens Ariel L.Raybuck Sung Hoon Cho Department of Pathology Microbiology&ImmunologyMolecular Pathogenesis DivisionVanderbilt University Medical CenterNashvilleTN37232USA Department of Medicine Rheumatology&Immunology DivisionVanderbilt University Medical CenterNashvilleTN37232USA Cancer Biology Program Vanderbilt UniversityNashvilleTN37232USA Vanderbilt Institute of Infection Inflammationand ImmunologyNashvilleTN37232USA

The COVID pandemic has refreshed and expanded recognition of the vital role that sustained antibody(Ab)secretion plays in our immune defenses against microbes and of the importance of vaccines that elicit Ab protection against *** this backdrop,it is especially timely to review aspects of the molecular programming that govern how the cells that secrete Abs arise,persist,and meet the challenge of secreting vast amounts of these *** plasmablasts and plasma cells(PCs)are the primary sources of secreted Abs,the process leading to the existence of these cell types starts with naive B lymphocytes that proliferate and differentiate toward several potential *** each step,cells reside in specific microenvironments in which they not only receive signals from cytokines and other cell surface receptors but also draw on the interstitium for *** in turn influence flux through intermediary metabolism and sensor enzymes that regulate gene transcription,translation,and *** review will focus on nutrient supply and how sensor mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab *** findings of this group and others,sometimes exhibiting differences,will be summarized with regard to the journey to a distinctive metabolic program in PCs.

关键词： B lymphocyte Plasma cell Intermediary metabolism Glucose Glutamine Fatty acid Signal transduction

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Atezolizumab Plus Bevacizumab in Advanced HCC: Efficacy in NASH-Specific Etiology

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Gastroenterology 2023年第5期165卷 1308-1310页

作者： Josep M Llovet Mathias Heikenwalder Mount Sinai Liver Cancer Program Division of Liver Diseases Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York New York Translational Research in Hepatic Oncology Liver Unit IDIBAPS Hospital Clinic University of Barcelona Barcelona Catalonia Spain Institució Catalana de Recerca i Estudis Avançats (ICREA) Barcelona Catalonia Spain. Division of Chronic Inflammation and Cancer German Cancer Research Center Heidelberg (DKFZ) Heidelberg Germany The M3 Research Institute Medical Facutly Tübingen (MTF) Tübingen Germany.

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Quantitative Analysis of Colonic Epithelial Cell Aging in a Cell-cycle like Model: Changes in Nucleus and Cytoplasm Along the Crypt Axis

Quantitative Analysis of Colonic Epithelial Cell Aging in a ...

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Medical Imaging 2025: Digital and Computational Pathology

作者： Bao, Shunxing Wang, Yaohong Rudravaram, Gaurav Zhang, Rendong Deng, Ruining Yu, Xin Gao, Chenyu Li, Jia Li, Yike Roland, Joseph T. Zuo, Lianrui Liu, Qi Lau, Ken S. Coburn, Lori A. Wilson, Keith T. Landman, Bennett A. Huo, Yuankai Department of Electrical and Computer Engineering Vanderbilt University NashvilleTN United States Department of Anatomical Pathology UT MD Anderson Cancer Center HoustonTX United States Department of Computer Science Vanderbilt University NashvilleTN United States Department of Biostatistics Vanderbilt University Medical Center Nashville United States Department of Otolaryngology-Head and Neck Surgery Vanderbilt University Medical Center NashvilleTN United States Department of Surgery Vanderbilt University Medical Center NashvilleTN United States Department of Cell and Developmental Biology Vanderbilt University School of Medicine NashvilleTN United States Vanderbilt University Medical Center Division of Gastroenterology Hepatology and Nutrition Department of Medicine Nashville United States Vanderbilt University Medical Center Vanderbilt Center for Mucosal Inflammation and Cancer Nashville United States Vanderbilt University School of Medicine Program in Cancer Biology Nashville United States Veterans Affairs Tennessee Valley Healthcare System NashvilleTN United States Vanderbilt University Medical Center Department of Pathology Microbiology and Immunology NashvilleTN United States

ISBN: (纸本)9781510686045

Understanding epithelial cell aging in bowel tissue can provide critical insights into gastrointestinal (GI) health, potentially leading to improved diagnosis, treatment, and prevention strategies for various GI conditions. Despite the significance of cellular aging in the GI tract, previous studies have not quantified epithelial cell maturity development along the base-to-surface axis of colon crypts due to the labor-intensive nature of manual quantification and the lack of a clear definition of cellular age. Moreover, the process faces tremendous challenges when tissue is cut in 2D and examines results solely from one or a few biopsy cuts without reconstructing the full 3D space, as the original cell structure is 3D, leading to variability based on the cut angle. This research addresses these challenges by systematically analyzing the relationship between epithelial cell morphology and their position from the base to the surface in colon crypt tissue. Our approach involves using multiplex immunofluorescence (MxIF) imaging for cell nuclei segmentation, identifying the potential full longitudinal cut, and manually annotating the surface and base of the colon crypts. By analyzing the epithelial cells, we create density maps to investigate the relationship between nucleus size and the surface-to-base distance ratio, defining this ratio as cell age. We also examine the nucleus-to-cytoplasm (N/C) ratio in relation to cell age. For the statistical analysis, we use a robust linear regression model to remove outliers and a random effects model for the final regression. Our results show a decreasing trend in both the N/C ratio and nucleus size as epithelial cells move from the base to the surface. These findings provide a quantitative pipeline for single-cell profiling in a spatial manner, facilitating broader analysis of epithelial cell aging and its implications for GI health. © 2025 SPIE.

关键词： Linear regression

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Evaluation of resazurin phenoxazine dye as a highly sensitive cell viability potency assay for natural killer cell-derived extracellular vesicle-based cancer biotherapeutics

Journal of Extracellular Biology

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Journal of Extracellular Biology 2024年第7期3卷 e166页

作者： St-Denis-Bissonnette, Frederic Qiu, Shirley Cummings, Sarah E. Kirkby, Melanie Haile, Yohannes Wassmer, Sarah Muradia, Gauri Mehic, Jelica Stalker, Andrew Shrestha, Amit Ardolino, Michele Lee, Seung-Hwan Burger, Dylan Wang, Lisheng Lavoie, Jessie R. Biologic and Radiopharmaceutical Drugs Directorate Health Canada Ottawa Canada Department of Biochemistry Microbiology and Immunology University of Ottawa Ottawa Canada Department of Neuroscience Carleton University Ottawa Canada Centre for Infection Immunity and Inflammation University of Ottawa Ottawa Canada Cancer Therapeutics Program Ottawa Hospital Research Institute Ottawa Canada Kidney Research Centre Ottawa Hospital Research Institute Ottawa Canada Department of Cellular and Molecular Medicine University of Ottawa Ottawa Canada Regenerative Medicine Program Ottawa Hospital Research Institute Ottawa Canada

Natural killer cell-derived extracellular vesicles (NK-EVs) are candidate biotherapeutics against various cancers. However, standardised potency assays are necessary for a reliable assessment of NK-EVs' cytotoxicity. This study aims to thoroughly evaluate a highly sensitive resazurin phenoxazine-based cell viability potency assay (measurement of the cellular redox metabolism) for quantifying the cytotoxicity of NK-EVs against leukaemia K562 cells (suspension model) and breast cancer MDA-MB-231 cells (adherent model) in vitro. The assay was evaluated based on common analytical parameters setforth by regulatory guidelines, including specificity, selectivity,accuracy, precision, linearity, range and stability. Our results revealed that this resazurin-based cell viability potency assay reliably and reproducibly measured a dose-response of NK-EVs’ cytotoxic activity against both cancer models. The assay showed precision with 5% and 20% variation for intra-run and inter-run variability. The assay signal showed specificity and selectivity of NK-EVs against cancer target cells, as evidenced by the diminished viability of cancer cells following a 5-hour treatment with NK-EVs, without any detectable interference or background. The linearity analysis of target cancer cells revealed strong linearity for densities of 5000 K562 and 1000 MDA-MB-231 cells per test with a consistent range. Importantly, NK-EVs’ dose-response for cytotoxicity showed a strong correlation (|ρ| ∼ 0.8) with the levels of known cytotoxic factors associated with the NK-EVs’ corona (FasL, GNLY, GzmB, PFN and IFN-γ), thereby validating the accuracy of the assay. The assay also distinguished cytotoxicity changes in degraded NK-EVs, indicating the ability of the assay to detect the potential loss of sample integrity. Compared to other commonly reported bioassays (i.e., flow cytometry, cell counting, lactate dehydrogenase release assay, DNA-binding reporter assay and confluence assay), our results support this h

关键词： biotherapeutics cancer exosome extracellular vesicles (EVs) natural killer (NK) cells potency assay resazurin

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A novel supplement with yeast b-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice

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Journal of Integrative Medicine 2021年第5期19卷 439-450页

作者： Victor Abou Nehmi Gilson Masahiro Murata Ruan Carlos Macêdo de Moraes Gabriely Cristina AlvesLima Danielle Araujo De Miranda Katrin Radloff Raquel Galvao Figuerêdo Costa Joyce de Cassia Rosade Jesus Jéssica Alves De Freitas Nayara Izabel Viana Ruan Pimenta Katia Ramos Moreira Leite JoséPinhata Otoch Ana Flávia Marcal Pessoa Laboratory of Medical Investigation(LIM-26) Department of SurgeryUniversity of Sao Paulo Medical SchoolSao PauloSP 01246903Brazil Laboratory of Medical Investigation(LIM-29) Clinic Medical DepartmentUniversity of Sao Paulo Medical SchoolSao PauloSP 01246903Brazil Department of Physiology Escola Paulista de Medicina/Universidade Federal de Sao PauloSP 04023062Brazil Max Rubner-Institut Federal Research Institute of Nutrition and FoodKarlsruheBW 76131Germany Cancer and Inflammation Program Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892United States Laboratory of Medical Investigation(LIM-55) Urology DepartmentUniversity of Sao Paulo Medical SchoolSao PauloSP 01246903Brazil D'Or Institute for Research and Education RJ 22281-100Brazil Program in Anesthesiology Surgical Sciencesand Perioperative MedicineUniversity of Sao PauloSao PauloSP 01246903Brazil Brazilian Academic Consortium for Integrative Health(CABSIN) Natural Products CommitteeSao PauloSP 05449-070Brazil

Objective: To evaluate the synergic effects of a novel oral supplement formulation, containing prebiotics,yeast b-glucans, minerals and silymarin(Silybum marianum), on lipid and glycidic metabolism, inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced obese ***: After an acclimation period, 32 male C57 BL/6 mice were divided into the following groups:nonfat diet(NFD) vehicle, NFD supplemented, high-fat diet(HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally by gavage once a day during the last four weeks of the diet(28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of ***: After four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia,fat, and hepatic fibrosis levels. Additionally, proliferator-activated receptor-α, AMP-activated protein kinase-1α, peroxisome proliferator-activated receptor γ co-activator-1α, and mitochondrial transcription factor A expression levels were augmented;however, levels of inhibitor of nuclear factor-κB kinase subunit a and p65 nuclear factor-κB expression, and oxidative markers were reduced. Notably, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic–pituitary–adrenal axis immune interface status, was found to be modulated by the ***: We discovered that the novel supplement was able to modify different antioxidant, metabolic and inflammatory pathways, improving the energy homeostasis and inflammatory status, and consequently alleviated hepatic steatosis.

关键词： Supplement Silymarin Prebiotic Obese Mice Steatosis inflammation Mitochondrial biogenesis

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Single-cell RNA sequencing-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma

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Journal of Hepatology 2025年第6期82卷 1036-1049页

作者： Cappuyns, Sarah Piqué-Gili, Marta Esteban-Fabró, Roger Philips, Gino Balaseviciute, Ugne Pinyol, Roser Gris-Oliver, Albert Vandecaveye, Vincent Abril-Fornaguera, Jordi Montironi, Carla Bassaganyas, Laia Peix, Judit Zeitlhoefler, Marcus Mesropian, Agavni Huguet-Pradell, Júlia Haber, Philipp K. Figueiredo, Igor Ioannou, Giorgio Gonzalez-Kozlova, Edgar Mohr, Raphael Meyer, Tim Lachenmayer, Anja Marquardt, Jens U. Reeves, Helen L. Edeline, Julien Finkelmeier, Fabian Trojan, Jörg Galle, Peter R. Foerster, Friedrich Mínguez, Beatriz Montal, Robert Gnjatic, Sacha Pinato, David J. Heikenwalder, Mathias Verslype, Chris Van Cutsem, Eric Lambrechts, Diether Villanueva, Augusto Dekervel, Jeroen Llovet, Josep M. Digestive Oncology Department of Gastroenterology University Hospitals Leuven Leuven Belgium Laboratory of Clinical Digestive Oncology Department of Oncology KU Leuven Leuven Belgium Laboratory for Translational Genetics Department of Human Genetics KU Leuven Leuven Belgium VIB Centre for Cancer Biology Leuven Belgium Mount Sinai Liver Cancer Program (Divisions of Liver Diseases Department of Hematology/Oncology Department of Medicine) Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York United States Liver Cancer Translational Research Group Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Hospital Clínic Universitat de Barcelona Catalonia Barcelona Spain Radiology Department University Hospitals Leuven Leuven Belgium Laboratory of Translational MRI Department of Imaging and Pathology KU Leuven Leuven Belgium Pathology Department and Molecular Biology Core Hospital Clínic of Barcelona Barcelona Spain Institut de Génomique Fonctionnelle Univ. Montpellier CNRS INSERM Montpellier France Department of Surgery Campus Charité Mitte and Campus Virchow-Klinikum Charité-Universitätsmedizin Berlin Berlin 13353 Germany Department of Immunology and Immunotherapy Icahn School of Medicine at Mount Sinai New York NY United States Department of Surgery & Cancer Imperial College London Hammersmith Hospital London United Kingdom Department of Hepatology and Gastroenterology Charité - Universitätsmedizin Berlin Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM) Berlin Germany Research Department of Oncology UCL Cancer Institute University College London Royal Free Hospital London United Kingdom Department of Visceral Surgery and Medicine Inselspital Bern University Hospital University of Bern Bern Switzerland Department of Medicine I University Medical Center Schleswig Holstein Campus Lübeck Lübeck Germany Hepatopancreatobiliary Multidisciplinary Team Newcastle upon Tyne NHS Foundation Trust Freeman Hospital New

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit vs. resistance to atezo+bev. Methods: We harnessed the power of single-cell RNA sequencing in advanced HCC to derive gene expression signatures recapitulating 21 cell phenotypes. These signatures were applied to 422 RNA-sequencing samples of patients with advanced HCC treated with atezo+bev (n = 317) vs. atezolizumab (n = 47) or sorafenib (n = 58) as comparators. Results: We unveiled two distinct patterns of response to atezo+bev. First, an immune-mediated response characterised by the combined presence of CD8+ T effector cells and pro-inflammatory CXCL10+ macrophages, representing an immune-rich microenvironment. Second, a non-immune, angiogenesis-related response distinguishable by a reduced expression of the VEGF co-receptor neuropilin-1 (NRP1), a biomarker that specifically predicts improved OS upon atezo+bev vs. sorafenib (p = 0.039). Primary resistance was associated with an enrichment of immunosuppressive myeloid populations, namely CD14+ monocytes and TREM2+ macrophages, and Notch pathway activation. Based on these mechanistic insights we define “Immune-competent” and “Angiogenesis-driven” molecular subgroups, each associated with a significantly longer OS with atezo+bev vs. sorafenib (p of interaction = 0.027), and a “Resistant” subset. Conclusion: Our study unveils two distinct molecular subsets of clinical benefit to atezolizumab plus bevacizumab in advanced HCC (“Immune-competent” and “Angiogenesis-driven”) as well as the main traits of primary resistance to this therapy, thus providing a molecular framework to stratify patients based on clinical outcome and guiding potential strategies to overcome resistance. Impact and implications: Atezolizumab + bevacizumab (a

关键词： Advanced Hepatocellular Carcinoma Atezolizumab and bevacizumab Biomarkers of Response Primary Resistance Single-Cell RNA-Sequencing

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Multimodel preclinical platform predicts clinical response of melanoma to immunotherapy (vol 26, pg 781, 2020)

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NATURE MEDICINE 2021年第2期27卷 355-355页

作者： Perez-Guijarro, Eva Yang, Howard H. Araya, Romina E. El Meskini, Rajaa Michael, Helen T. Vodnala, Suman Kumar Marie, Kerrie L. Smith, Cari Chin, Sung Lam, Khiem C. Thorkelsson, Andres Iacovelli, Anthony J. Kulaga, Alan Fon, Anyen Michalowski, Aleksandra M. Hugo, Willy Lo, Roger S. Restifo, Nicholas P. Sharan, Shyam K. Van Dyke, Terry Goldszmid, Romina S. Ohler, Zoe Weaver Lee, Maxwell P. Day, Chi-Ping Merlino, Glenn Laboratory of Cancer Biology and Genetics Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA Cancer and Inflammation Program Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA Center for Advanced Preclinical Research Center for Cancer Research National Cancer Institute National Institutes of Health Frederick MD USA Mouse Cancer Genetics Program Center for Cancer Research National Cancer Institute National Institutes of Health Frederick MD USA Surgery Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA Laboratory Animal Science Program Leidos Biomedical Research Inc Frederick MD USA Division of Dermatology Department of Medicine University of California Los Angeles Los Angeles CA USA

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Identifying Cellular Neighborhood Phenotypes Differentiating Normal and Quiescent Crohn's Disease via MxIF

Identifying Cellular Neighborhood Phenotypes Differentiating...

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Medical Imaging 2025: Digital and Computational Pathology

作者： Rudravaram, Gaurav Bao, Shunxing Krishnan, Aravind R. Remedios, Lucas W. Kim, Michael E. Saunders, Adam M. Liu, Qi Lau, Ken S. Roland, Joseph T. Washington, Mary K. Coburn, Lori A. Wilson, Keith T. Huo, Yuankai Landman, Bennett A. Department of Electrical and Computer Engineering Vanderbilt University NashvilleTN United States Department of Computer Science Vanderbilt University NashvilleTN United States Division of Gastroenterology Hepatology and Nutrition Department of Medicine Vanderbilt University Medical Center NashvilleTN United States Vanderbilt Center for Mucosal Inflammation and Cancer Vanderbilt University Medical Center NashvilleTN United States Program in Cancer Biology Vanderbilt University School of Medicine NashvilleTN United States Veterans Affairs Tennessee Valley Healthcare System NashvilleTN United States Department of Pathology Microbiology and Immunology Vanderbilt University Medical Center NashvilleTN United States Center for Quantitative Sciences Vanderbilt University Medical Center NashvilleTN United States Epithelial Biology Center Vanderbilt University Medical Center NashvilleTN United States Department of Cell and Developmental Biology Vanderbilt University School of Medicine NashvilleTN United States Vanderbilt University Department of Biomedical Engineering Nashville United States Department of Biostatistics Vanderbilt University Medical Center Nashville United States

ISBN: (纸本)9781510686045

Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract characterized by alternating periods of activity and remission. This study investigates whether the cellular environments of quiescent (inactive disease) and normal tissues show similarities or differences, exploring potential residual effects from disease and tissue recovery patterns. While active CD can typically be characterized by high neutrophil density, whereas quiescent tissues present less pronounced inflammatory markers. This study leverages multiplexed immunofluorescence (MxIF) data to examine the distributions and patterns of various nuclei subtypes in quiescent versus normal tissues, aiming to determine how similar or different these tissues are in the absence of active inflammation. In our study, we analyze four tissue samples labeled as normal and five as quiescent from CD patients, as determined by a pathologist. We use rigid and deformable registration of MxIF images to analyze these tissues in a unified space and classify the nuclei into 13 subtypes. Using a KD tree, we identify the 10 nearest neighbors for each nucleus, building a combined distance-weighted neighborhood matrix representing both normal and quiescent tissues. We projected these neighborhoods into 2 dimensions using t-distributed stochastic nearest neighbor(t-SNE), clustered them, and calculated the enrichment for each subtype between normal and quiescent states within each of 20 and 40 clusters. In the 20-cluster analysis, we find monocytes enrich in one cluster and leukocytes enrich in two clusters for normal and quiescent tissues respectively. For the 40-cluster analysis, we observe monocytes, macrophages, and leukocytes enrich in one cluster each in normal tissues, and in the quiescent condition, one cluster enriched with enteroendocrine cells, and two clusters enriched with leukocytes. The results were statistically significant as determined by a chi-squared test (p © 2025 SPIE.

关键词： Tissues White blood cells Diseases and disorders Biological samples Matrices Statistical analysis Image segmentation Image registration Critical dimension metrology inflammation

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