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Importance of surface charge of soot nanoparticles in determining inhalation toxicity in mice

Environmental Science and Pollution Research 2023年第7期30卷 18985-18997页

作者： Hsiao, Ta-Chih Han, Chia-Li Yang, Tzu-Ting Lee, Yueh-Lun Shen, Yu-Fang Jheng, Yu-Teng Lee, Chii-Hong Chang, Jer-Hwa Chung, Kian Fan Kuo, Han-Pin Chuang, Hsiao-Chi Graduate Institute of Environmental Engineering National Taiwan University Taipei Taiwan Master Program in Clinical Genomics and Proteomics College of Pharmacy Taipei Medical University Taipei Taiwan Department of Environmental Engineering and Health Yuanpei University of Medical Technology Hsin Chu City Taiwan Department of Microbiology and Immunology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Environmental Engineering National Center University Tauyoun Taiwan Genome and Systems Biology Degree Program Academia Sinica and National Taiwan University Taipei Taiwan Department of Pathology Taipei City Hospital Heping Fuyou Branch Taipei Taiwan School of Respiratory Therapy College of Medicine Taipei Medical University Taipei Taiwan Division of Pulmonary Medicine Department of Internal Medicine Wan Fang Hospital Taipei Medical University Taipei Taiwan National Heart and Lung Institute Imperial College London London United Kingdom Division of Pulmonary Medicine Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Division of Pulmonary Medicine Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Cell Physiology and Molecular Image Research Center Wan Fang Hospital Taipei Medical University Taipei Taiwan

Physicochemical properties of nanoparticles are important in regulating nanoparticle toxicity;however, the contribution of nanoparticle charge remains unclear. The objective of this study was to investigate the pulmonary effects of inhalation of charged soot nanoparticles. We established a stably charged nanoparticle generation system for whole-body exposure in BALB/c mice, which produced positively charged, negatively charged, and neutral soot nanoparticles in a wide range of concentrations. After a 7-day exposure, pulmonary toxicity was assessed, together with proteomics analysis. The charged soot nanoparticles on average carried 1.17–1.35 electric charges, and the sizes for nanoparticles under different charging conditions were all fixed at 69 ~ 72 nm. We observed that charged soot nanoparticles induced cytotoxic LDH and increased lung permeability, with the release of 8-isoprostane and caspase-3 and systemic IL-6 in mice, especially for positively charged soot nanoparticles. Next, we observed that positive-charged soot nanoparticles upregulated Eif2, Eif4, sirtuin, mammalian target of rapamycin (mTOR), peroxisome proliferator-activated receptors (PPAR), and HIPPO-related signaling pathways in the lungs compared with negatively charged soot nanoparticles. HIF1α, sirt1, E-cadherin, and Yap were increased in mice’s lungs by positively charged soot nanoparticle exposure. In conclusion, carbonaceous nanoparticles carrying electric ions, especially positive-charged, are particularly toxic when inhaled and should be of concern in terms of pulmonary health protection. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

关键词： Nanoparticles

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Loss of TET2 Uncouples Proliferative and Effector Functions in CAR T cells

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BLOOD 2020年 136卷 1-1页

作者： Jain, Nayan Zhao, Zeguo Iyer, Archana S. Lopez, Michael Feucht, Judith Koche, Richard P. Zhan, Yingqian Sadelain, Michel Louis V. Gerstner Jr. Graduate School of Biomedical Sciences Memorial Sloan Kettering Cancer Center New York City NY Center for Cell Engineering and Immunology Program Memorial Sloan Kettering Cancer Center New York City NY Center for Epigenetics Research Memorial Sloan Kettering Cancer Center New York City NY

Chimeric antigen receptor (CAR) T cells have opened a new paradigm for the treatment of leukemia and lymphoma. Their production, however, is laborious, requiring tens of millions of CAR T cells per infusion. This constraint could be significantly alleviated if safe and more efficacious T cells could be generated. In a patient with chronic lymphocytic leukemia, treated with anti-CD19 CAR T cells, a recent report described the emergence of a single T cell clone that at its expansion peak accounted for 94% of circulating CAR T cells, coinciding with the development of cytokine release syndrome and tumor regression (Fraietta et. al. Nature 2018). Insertional mutagenesis in this T cell had disrupted an allele of TET2 , an epigenetic regulator mediating the oxidation of 5-methylcytosine. The other allele appeared to bear an inherited hypomorphic variant, resulting in the near complete loss of TET2 function in this clone. To understand the mechanisms accounting for this chance clinical finding, we investigated the effect of TET2 loss in human T cells engineered to express different chimeric receptors. Using CRISPR/Cas9, we edited TET2 in T cells engineered to express a CD19-specific second-generation CAR encompassing the costimulatory domain of either CD28 or 4-1BB (Rv-1928z and Rv-19BBz). TET2 disruption enhanced the in vivo anti-tumor activity of Rv-19BBz but not Rv-1928z CAR T cells tested under stress test conditions using limiting CAR T cell doses (as previously described in a human B cell acute lymphoblastic leukemia (B-ALL) NALM6 model, Zhao et. al. Cancer cell 2015). Since Rv-1928z induces potent effector differentiation but limited persistence compared to Rv-19BBz, we hypothesized that loss of TET2 could amplify the expansion and persistence of 4-1BB-costimulated T cells but not override the differentiation program imparted by Rv-1928z. To test this hypothesis, we utilized two orthogonal approaches known to limit exhaustion and increase persistence of CD28-costimu

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Increased risk of cancer in dogs and humans: A consequence of recent extension of lifespan beyond evolutionarily determined limitations?

Aging and Cancer

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Aging and Cancer 2022年第1期3卷 3-19页

作者： Sarver, Aaron L. Makielski, Kelly M. DePauw, Taylor A. Schulte, Ashley J. Modiano, Jaime F. Masonic Cancer Center University of Minnesota Minneapolis MN United States Institute for Health Informatics University of Minnesota Minneapolis MN United States Animal Cancer Care and Research Program University of Minnesota St. Paul MN United States Department of Veterinary Clinical Sciences College of Veterinary Medicine University of Minnesota St. Paul MN United States Department of Laboratory Medicine and Pathology School of Medicine University of Minnesota Minneapolis MN United States Center for Immunology University of Minnesota Minneapolis MN United States Stem Cell Institute University of Minnesota Minneapolis MN United States Institute for Engineering in Medicine University of Minnesota Minneapolis MN United States

Cancer is among the most common causes of death for dogs (and cats) and humans in the developed world, even though it is uncommon in wildlife and other domestic animals. We provide a rationale for this observation based on recent advances in our understanding of the evolutionary basis of cancer. Over the course of evolutionary time, species have acquired and fine-tuned adaptive cancer-protective mechanisms that are intrinsically related to their energy demands, reproductive strategies, and expected lifespan. These cancer-protective mechanisms are general across species and/or specific to each species and their niche, and they do not seem to be limited in diversity. The evolutionarily acquired cancer-free longevity that defines a species’ life history can explain why the relative cancer risk, rate, and incidence are largely similar across most species in the animal kingdom despite differences in body size and life expectancy. The molecular, cellular, and metabolic events that promote malignant transformation and cancerous growth can overcome these adaptive, species-specific protective mechanisms in a small proportion of individuals, while independently, some individuals in the population might achieve exceptional longevity. In dogs and humans, recent dramatic alterations in healthcare and social structures have allowed increasing numbers of individuals in both species to far exceed their species-adapted longevities (by two to four times) without allowing the time necessary for compensatory natural selection. In other words, the cancer-protective mechanisms that restrain risk at comparable levels to other species for their adapted lifespan are incapable of providing cancer protection over this recent, drastic, and widespread increase in longevity. © 2022 The Authors. Aging and Cancer published by Wiley Periodicals, Inc.

关键词： cancer risk cancer-protective mechanisms evolution longevity

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Author Correction: Generation of T-cell-receptor-negative CD8αβ-positive CAR T cells from T-cell-derived induced pluripotent stem cells

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Nature biomedical engineering 2024年第11期8卷 1500页

作者： Sjoukje J C van der Stegen Pieter L Lindenbergh Roseanna M Petrovic Hongyao Xie Mame P Diop Vera Alexeeva Yuzhe Shi Jorge Mansilla-Soto Mohamad Hamieh Justin Eyquem Annalisa Cabriolu Xiuyan Wang Ramzey Abujarour Tom Lee Raedun Clarke Bahram Valamehr Maria Themeli Isabelle Riviere Michel Sadelain Center for Cell Engineering Memorial Sloan Kettering Cancer Center New York NY USA. Immunology Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY USA. Department of Hematology Cancer Center Amsterdam Amsterdam UMC VU Amsterdam Amsterdam the Netherlands. Gladstone-UCSF Institute of Genomic Immunology Gladstone Institutes San Francisco CA USA. Cell Therapy and Cell Engineering Facility Memorial Sloan Kettering Cancer Center New York NY USA. Fate Therapeutics Inc San Diego CA USA. Center for Cell Engineering Memorial Sloan Kettering Cancer Center New York NY USA. m-sadelain@***. Immunology Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY USA. m-sadelain@***.

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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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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher E.Mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Data-driven Nucleus Subclassification on Colon H&E using Style-transferred Digital Pathology

arXiv

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arXiv 2024年

作者： Remedios, Lucas W. Bao, Shunxing Remedios, Samuel W. Lee, Ho Hin Cai, Leon Y. Li, Thomas Deng, Ruining Newlin, Nancy R. Saunders, Adam M. Cui, Can Li, Jia Liu, Qi Lau, Ken S. Roland, Joseph T. Washington, Mary K. Coburn, Lori A. Wilson, Keith T. Huo, Yuankai Landman, Bennett A. Vanderbilt University Department of Computer Science Nashville United States Vanderbilt University Department of Electrical and Computer Engineering Nashville United States Johns Hopkins University Department of Computer Science Baltimore United States National Institutes of Health Department of Radiology and Imaging Sciences Bethesda United States Vanderbilt University Department of Biomedical Engineering Nashville United States Vanderbilt University Medical Center Department of Biostatistics Nashville United States Vanderbilt University Medical Center Center for Quantitative Sciences Nashville United States Vanderbilt University Medical Center Epithelial Biology Center Nashville United States Vanderbilt University School of Medicine Department of Cell and Developmental Biology Nashville 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

Purpose: cells are building blocks for human physiology;consequently, understanding the way cells communicate, co-locate, and interrelate is essential to furthering our understanding of how the body functions in both health and disease. Hematoxylin and eosin (H&E) is the standard stain used in histological analysis of tissues. Microscope slides of H&E-stained tissues are widely available in both clinical and research settings. While H&E is ubiquitous and reveals tissue microanatomy, the classification and tracking of cell subtypes often requires expert knowledge and the use of specialized stains, such as immunofluorescence staining. To reduce both the manual annotation burden and reliance on specialized staining technologies, artificial intelligence has been proposed for the automatic classification of cell types on H&E slides. For example, the recent Colon Nucleus Identification and Classification (CoNIC) Challenge focused on labeling 6 cell types on imaging of H&E stains from the human colon. However, this is a very small fraction of the number of potential cell subtypes within the intestines. Specifically, the CoNIC Challenge was unable to classify epithelial subtypes (progenitor, enteroendocrine, goblet), lymphocyte subtypes (B, helper T, cytotoxic T), and connective subtypes (fibroblasts). To approach this problem, we propose to use inter-modality learning to label previously un-labelable cell types on H&E. Approach: We take advantage of the cell classification information inherent in whole slide images (WSIs) of multiplexed immunofluorescence (MxIF) histology to create cell level annotations for 14 subclasses. We performed style transfer on the same MxIF tissues to synthesize realistic virtual H&E which we paired with the MxIF-derived cell subclassification labels. We evaluated the efficacy of using a supervised learning scheme where the input was realistic-quality virtual H&E and the labels were MxIF-derived cell subclasses. We assessed our model on a testing

关键词： Tissue

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Nucleus subtype classification using inter-modality learning

arXiv

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arXiv 2024年

作者： Remedios, Lucas W. Bao, Shunxing Remedios, Samuel W. Lee, Ho Hin Cai, Leon Y. Li, Thomas Deng, Ruining Cui, Can Li, Jia Liu, Qi Lau, Ken S. Roland, Joseph T. Washington, Mary K. Coburn, Lori A. Wilson, Keith T. Huo, Yuankai Landman, Bennett A. Vanderbilt University Department of Computer Science Nashville United States Vanderbilt University Department of Electrical and Computer Engineering Nashville United States Johns Hopkins University Department of Computer Science Baltimore United States National Institutes of Health Department of Radiology and Imaging Sciences Bethesda United States Vanderbilt University Department of Biomedical Engineering Nashville United States Vanderbilt University Medical Center Department of Biostatistics Nashville United States Vanderbilt University Medical Center Center for Quantitative Sciences Nashville United States Vanderbilt University Medical Center Epithelial Biology Center Nashville United States Vanderbilt University School of Medicine Department of Cell and Developmental Biology Nashville 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

Understanding the way cells communicate, co-locate, and interrelate is essential to understanding human physiology. Hematoxylin and eosin (H&E) staining is ubiquitously available both for clinical studies and research. The Colon Nucleus Identification and Classification (CoNIC) Challenge has recently innovated on robust artificial intelligence labeling of six cell types on H&E stains of the colon. However, this is a very small fraction of the number of potential cell classification types. Specifically, the CoNIC Challenge is unable to classify epithelial subtypes (progenitor, endocrine, goblet), lymphocyte subtypes (B, helper T, cytotoxic T), or connective subtypes (fibroblasts, stromal). In this paper, we propose to use inter-modality learning to label previously un-labelable cell types on virtual H&E. We leveraged multiplexed immunofluorescence (MxIF) histology imaging to identify 14 subclasses of cell types. We performed style transfer to synthesize virtual H&E from MxIF and transferred the higher density labels from MxIF to these virtual H&E images. We then evaluated the efficacy of learning in this approach. We identified helper T and progenitor nuclei with positive predictive values of 0.34 ± 0.15 (prevalence 0.03 ± 0.01) and 0.47 ± 0.1 (prevalence 0.07 ± 0.02) respectively on virtual H&E. This approach represents a promising step towards automating annotation in digital pathology. © 2024, CC BY.

关键词： cell culture

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Early experience using salvage radiotherapy for relapsed/refractory non-Hodgkin lymphomas after CD19 chimeric antigen receptor (CAR) T cell therapy

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BRITISH JOURNAL OF HAEMATOLOGY 2020年第1期190卷 45-51页

作者： [Anonymous] Department of Radiation Oncology Memorial Sloan Kettering Cancer Center New York NY USA Center for Cell Engineering and Immunology Program Memorial Sloan Kettering Cancer Center New York NY USA Department of Radiation Oncology Washington University School of Medicine Saint Louis MO USA Department of Medicine Lymphoma Service Memorial Sloan Kettering Cancer Center New York NY USA Department of Medicine Center for Cellular Therapeutics Memorial Sloan Kettering Cancer Center New York NY USA Department of Medicine Adult Bone Marrow Transplant Service Memorial Sloan Kettering Cancer Center New York NY USA

Summary Radiotherapy is potentially an important salvage strategy post‐chimeric antigen receptor T cell therapy (CART), but limited data exist. We reviewed 14 patients treated with salvage radiation post‐CART progression (SRT). Most received SRT for first post‐CART relapse (71%) to sites previously PET‐avid pre‐CART (79%). Median overall survival (OS) post‐SRT was 10 months. Post‐SRT, six localized relapses achieved 100% response (3 = complete, 3 = partial), with improved freedom from subsequent relapse (P = 0·001) and OS (P = 0·004) compared to advanced stage relapses. Three were bridged to allogeneic transplantation; at analysis, all were alive/NED. SRT has diverse utility and can integrate with novel agents or transplantation to attempt durable remissions.

关键词： chimeric antigen receptor T cells CAR T cells radiotherapy salvage therapy diffuse large B cell lymphoma relapsed/refractory

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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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