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  1. Article ; Online: Graph Perceiver Network for Lung Tumor and Bronchial Premalignant Lesion Stratification from Histopathology.

    Gindra, Rushin H / Zheng, Yi / Green, Emily J / Reid, Mary E / Mazzilli, Sarah A / Merrick, Daniel T / Burks, Eric J / Kolachalama, Vijaya B / Beane, Jennifer E

    The American journal of pathology

    2024  

    Abstract: Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous cell carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. In this ... ...

    Abstract Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous cell carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. In this context, we present a novel computational approach, the Graph Perceiver Network, leveraging hematoxylin and eosin-stained whole slide images to stratify endobronchial biopsies of PMLs across a spectrum from normal to tumor lung tissues. The Graph Perceiver Network outperforms existing frameworks in classification accuracy predicting LUSC, lung adenocarcinoma, and nontumor (normal) lung tissue on The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium datasets containing lung resection tissues while efficiently generating pathologist-aligned, class-specific heat maps. The network was further tested using endobronchial biopsies from two data cohorts, containing normal to carcinoma in situ histology, and it demonstrated a unique capability to differentiate carcinoma in situ lung squamous PMLs based on their progression status to invasive carcinoma. The network may have utility in stratifying PMLs for chemoprevention trials or more aggressive follow-up.
    Language English
    Publishing date 2024-04-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2024.03.009
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  2. Article: Repetitive head impacts induce neuronal loss and neuroinflammation in young athletes.

    Butler, Morgane L M D / Pervaiz, Nida / Ypsilantis, Petra / Wang, Yichen / Cammasola Breda, Julia / Mazzilli, Sarah / Nicks, Raymond / Spurlock, Elizabeth / Hefti, Marco M / Huber, Bertrand R / Alvarez, Victor E / Stein, Thor D / Campbell, Joshua D / McKee, Ann C / Cherry, Jonathan D

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Repetitive head impacts (RHI) sustained from contact sports are the largest risk factor for chronic traumatic encephalopathy (CTE). Currently, CTE can only be diagnosed after death and the multicellular cascade of events that trigger initial ... ...

    Abstract Repetitive head impacts (RHI) sustained from contact sports are the largest risk factor for chronic traumatic encephalopathy (CTE). Currently, CTE can only be diagnosed after death and the multicellular cascade of events that trigger initial hyperphosphorylated tau (p-tau) deposition remain unclear. Further, the symptoms endorsed by young individuals with early disease are not fully explained by the extent of p-tau deposition, severely hampering development of therapeutic interventions. Here, we show that RHI exposure associates with a multicellular response in young individuals (<51 years old) prior to the onset of CTE p-tau pathology that correlates with number of years of RHI exposure. Leveraging single nucleus RNA sequencing of tissue from 8 control, 9 RHI-exposed, and 11 low stage CTE individuals, we identify SPP1+ inflammatory microglia, angiogenic and inflamed endothelial cell profiles, reactive astrocytes, and altered synaptic gene expression in excitatory and inhibitory neurons in all individuals with exposure to RHI. Surprisingly, we also observe a significant loss of cortical sulcus layer 2/3 neurons in contact sport athletes compared to controls independent of p-tau pathology. These results provide robust evidence that multiple years of RHI exposure is sufficient to induce lasting cellular alterations that may underlie p-tau deposition and help explain the early clinical symptoms observed in young former contact sport athletes. Furthermore, these data identify specific cellular responses to repetitive head impacts that may direct future identification of diagnostic and therapeutic strategies for CTE.
    Language English
    Publishing date 2024-03-28
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.26.586815
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  3. Article ; Online: Convergence of YAP/TAZ, TEAD and TP63 activity is associated with bronchial premalignant severity and progression.

    Ning, Boting / Tilston-Lunel, Andrew M / Simonetti, Justice / Hicks-Berthet, Julia / Matschulat, Adeline / Pfefferkorn, Roxana / Spira, Avrum / Edwards, Matthew / Mazzilli, Sarah / Lenburg, Marc E / Beane, Jennifer E / Varelas, Xaralabos

    Journal of experimental & clinical cancer research : CR

    2023  Volume 42, Issue 1, Page(s) 116

    Abstract: Background: Bronchial premalignant lesions (PMLs) are composed primarily of cells resembling basal epithelial cells of the airways, which through poorly understood mechanisms have the potential to progress to lung squamous cell carcinoma (LUSC). Despite ...

    Abstract Background: Bronchial premalignant lesions (PMLs) are composed primarily of cells resembling basal epithelial cells of the airways, which through poorly understood mechanisms have the potential to progress to lung squamous cell carcinoma (LUSC). Despite ongoing efforts that have mapped gene expression and cell diversity across bronchial PML pathologies, signaling and transcriptional events driving malignancy are poorly understood. Evidence has suggested key roles for the Hippo pathway effectors YAP and TAZ and associated TEAD and TP63 transcription factor families in bronchial basal cell biology and LUSC. In this study we examine the functional association of YAP/TAZ, TEADs and TP63 in bronchial epithelial cells and PMLs.
    Methods: We performed RNA-seq in primary human bronchial epithelial cells following small interfering RNA (siRNA)-mediated depletion of YAP/TAZ, TEADs or TP63, and combined these data with ChIP-seq analysis of these factors. Directly activated or repressed genes were identified and overlapping genes were profiled across gene expression data obtained from progressive or regressive human PMLs and across lung single cell RNA-seq data sets.
    Results: Analysis of genes regulated by YAP/TAZ, TEADs, and TP63 in human bronchial epithelial cells revealed a converged transcriptional network that is strongly associated with the pathological progression of bronchial PMLs. Our observations suggest that YAP/TAZ-TEAD-TP63 associate to cooperatively promote basal epithelial cell proliferation and repress signals associated with interferon responses and immune cell communication. Directly repressed targets we identified include the MHC Class II transactivator CIITA, which is repressed in progressive PMLs and associates with adaptive immune responses in the lung. Our findings provide molecular insight into the control of gene expression events driving PML progression, including those contributing to immune evasion, offering potential new avenues for lung cancer interception.
    Conclusions: Our study identifies important gene regulatory functions for YAP/TAZ-TEAD-TP63 in the early stages of lung cancer development, which notably includes immune-suppressive roles, and suggest that an assessment of the activity of this transcriptional complex may offer a means to identify immune evasive bronchial PMLs and serve as a potential therapeutic target.
    MeSH term(s) Humans ; Carcinoma, Squamous Cell ; Gene Expression Regulation ; Lung Neoplasms/genetics ; Precancerous Conditions/genetics ; Signal Transduction ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; YAP-Signaling Proteins ; TEA Domain Transcription Factors
    Chemical Substances TP63 protein, human ; Transcription Factors ; Tumor Suppressor Proteins ; YAP-Signaling Proteins ; WWTR1 protein, human ; TEA Domain Transcription Factors
    Language English
    Publishing date 2023-05-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 803138-1
    ISSN 1756-9966 ; 0392-9078
    ISSN (online) 1756-9966
    ISSN 0392-9078
    DOI 10.1186/s13046-023-02674-5
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    Zs.A 2065: Show issues Location:
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  4. Article ; Online: Association of vaping with decreased vascular endothelial growth factor expression and decreased microvessel density in cutaneous wound healing tissue in rats.

    Jaleel, Zaroug / Blasberg, Elizabeth / Troiano, Chelsea / Montanaro, Paige / Mazzilli, Sarah / Gertje, Hans Peter / Crossland, Nicholas A / Platt, Michael / Spiegel, Jeffrey

    Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

    2021  Volume 29, Issue 6, Page(s) 1024–1034

    Abstract: Vaping is suggested to be a risk factor for poor wound healing akin to smoking. However, the molecular and histologic mechanisms underlying this postulation remain unknown. Our study sought to compare molecular and histologic changes in cutaneous flap ... ...

    Abstract Vaping is suggested to be a risk factor for poor wound healing akin to smoking. However, the molecular and histologic mechanisms underlying this postulation remain unknown. Our study sought to compare molecular and histologic changes in cutaneous flap and non-flap tissue between vaping, smoking and control cohorts. Animal study of 15 male Sprague-Dawley rats was randomized to three cohorts: negative control (n = 5), e-cigarette (n = 5) and cigarette (n = 5) and exposed to their respective treatments with serum cotinine monitoring. After 30 days, random pattern flaps were raised and healed for 2 weeks after which skin punch biopsies of flap and non-flap tissues were collected for quantitative-reverse transcription-polymerase chain reaction of three selected wound healing genes (transforming growth factor β [TGF-β], vascular endothelial growth factor [VEGF], matrix metalloproteinase-1 [MMP-1]); then, immunohistochemistry for CD68 expression, α-smooth muscle actin looking at microvessel density (MVD) and in situ hybridization to localize VEGF production were undertaken. In flap tissue, vaping (mean[SEM]) (0.61[0.07]) and smoking (0.70[0.04]) were associated with decreased fold change of VEGF expression compared with controls (0.91[0.03]) (p < 0.05, p < 0.05, respectively). In non-flap tissue, only vaping was associated with decreased VEGF expression (mean[SEM]) (0.81[0.07]), compared with controls (1.17[0.10]) (p < 0.05) with expression primarily localized to basal keratinocytes and dermal capillaries. Immunohistochemistry showed decreased MVD in smoking (0.27[0.06]) and vaping (0.26[0.04]) flap tissue compared to matched controls (0.65[0.14]) (p < 0.05, p < 0.05, respectively) and decreased areas of fibrosis compared with controls on gross histology. Vaping and smoking were similarly associated with decreased VEGF expression, MVD and fibrotic changes in flap tissue. The results suggest attenuated angiogenesis via decreased VEGF expression as a mechanism for poor wound healing in vaping-exposed rats.
    MeSH term(s) Animals ; Electronic Nicotine Delivery Systems ; Male ; Microvascular Density ; Rats ; Rats, Sprague-Dawley ; Vaping ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; Wound Healing
    Chemical Substances Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
    Language English
    Publishing date 2021-06-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1174873-4
    ISSN 1524-475X ; 1067-1927
    ISSN (online) 1524-475X
    ISSN 1067-1927
    DOI 10.1111/wrr.12945
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    Zs.A 3890: Show issues Location:
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  5. Article ; Online: Elevated T cell repertoire diversity is associated with progression of lung squamous cell premalignant lesions.

    Maoz, Asaf / Merenstein, Carter / Koga, Yusuke / Potter, Austin / Gower, Adam C / Liu, Gang / Zhang, Sherry / Liu, Hanqiao / Stevenson, Christopher / Spira, Avrum / Reid, Mary E / Campbell, Joshua D / Mazzilli, Sarah A / Lenburg, Marc E / Beane, Jennifer

    Journal for immunotherapy of cancer

    2022  Volume 9, Issue 9

    Abstract: Objective: The immune response to invasive carcinoma has been the focus of published work, but little is known about the adaptive immune response to bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma. This study was ... ...

    Abstract Objective: The immune response to invasive carcinoma has been the focus of published work, but little is known about the adaptive immune response to bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma. This study was designed to characterize the T cell receptor (TCR) repertoire in PMLs and its association with clinical, pathological, and molecular features.
    Methods: Endobronchial biopsies (n=295) and brushings (n=137) from high-risk subjects (n=50), undergoing lung cancer screening at approximately 1-year intervals via autofluorescence bronchoscopy and CT, were profiled by RNA-seq. We applied the TCR Repertoire Utilities for Solid Tissue/Tumor tool to the RNA-seq data to identify TCR CDR3 sequences across all samples. In the biopsies, we measured the correlation of TCR diversity with previously derived immune-associated PML transcriptional signatures and PML outcome. We also quantified the spatial and temporal distribution of shared and clonally expanded TCRs. Using the biopsies and brushes, the ratio of private (ie, found in one patient only) and public (ie, found in two or more patients) TCRs was quantified, and the CDR3 sequences were compared with those found in curated databases with known antigen specificities.
    Results: We detected 39,303 unique TCR sequences across all samples. In PML biopsies, TCR diversity was negatively associated with a transcriptional signature of T cell mediated immune activation (p=4e-4) associated with PML outcome. Additionally, in lesions of the proliferative molecular subtype, TCR diversity was decreased in regressive versus progressive/persistent PMLs (p=0.045). Within each patient, TCRs were more likely to be shared between biopsies sampled at the same timepoint than biopsies sampled at the same anatomic location at different times. Clonally expanded TCRs, within a biopsied lesion, were more likely to be expanded at future time points than non-expanded clones. The majority of TCR sequences were found in a single sample, with only 3396 (8.6%) found in more than one sample and 1057 (2.7%) found in two or more patients (ie, public); however, when compared with a public database of CDR3 sequences, 4543 (11.6%) of TCRs were identified as public. TCRs with known antigen specificities were enriched among public TCRs (p<0.001).
    Conclusions: Decreased TCR diversity may reflect nascent immune responses that contribute to PML elimination. Further studies are needed to explore the potential for immunoprevention of PMLs.
    MeSH term(s) Disease Progression ; Female ; Humans ; Lung Neoplasms/genetics ; Male ; Neoplasms, Squamous Cell/genetics ; T-Lymphocytes/immunology
    Language English
    Publishing date 2022-05-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2021-002647
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  6. Article ; Online: Single-Cell Characterization of Pulmonary Nodules Implicates Suppression of Immunosurveillance across Early Stages of Lung Adenocarcinoma.

    Yanagawa, Jane / Tran, Linh M / Salehi-Rad, Ramin / Lim, Raymond J / Dumitras, Camelia / Fung, Eileen / Wallace, William D / Prosper, Ashley E / Fishbein, Gregory / Shea, Conor / Hong, Rui / Kahangi, Bitta / Deng, John J / Gower, Adam C / Liu, Bin / Campbell, Joshua D / Mazzilli, Sarah A / Beane, Jennifer E / Kadara, Humam /
    Lenburg, Marc E / Spira, Avrum E / Aberle, Denise R / Krysan, Kostyantyn / Dubinett, Steven M

    Cancer research

    2023  Volume 83, Issue 19, Page(s) 3305–3319

    Abstract: A greater understanding of molecular, cellular, and immunological changes during the early stages of lung adenocarcinoma development could improve diagnostic and therapeutic approaches in patients with pulmonary nodules at risk for lung cancer. To ... ...

    Abstract A greater understanding of molecular, cellular, and immunological changes during the early stages of lung adenocarcinoma development could improve diagnostic and therapeutic approaches in patients with pulmonary nodules at risk for lung cancer. To elucidate the immunopathogenesis of early lung tumorigenesis, we evaluated surgically resected pulmonary nodules representing the spectrum of early lung adenocarcinoma as well as associated normal lung tissues using single-cell RNA sequencing and validated the results by flow cytometry and multiplex immunofluorescence (MIF). Single-cell transcriptomics revealed a significant decrease in gene expression associated with cytolytic activities of tumor-infiltrating natural killer and natural killer T cells. This was accompanied by a reduction in effector T cells and an increase of CD4+ regulatory T cells (Treg) in subsolid nodules. An independent set of resected pulmonary nodules consisting of both adenocarcinomas and associated premalignant lesions corroborated the early increment of Tregs in premalignant lesions compared with the associated normal lung tissues by MIF. Gene expression analysis indicated that cancer-associated alveolar type 2 cells and fibroblasts may contribute to the deregulation of the extracellular matrix, potentially affecting immune infiltration in subsolid nodules through ligand-receptor interactions. These findings suggest that there is a suppression of immune surveillance across the spectrum of early-stage lung adenocarcinoma.
    Significance: Analysis of a spectrum of subsolid pulmonary nodules by single-cell RNA sequencing provides insights into the immune regulation and cell-cell interactions in the tumor microenvironment during early lung tumor development.
    MeSH term(s) Humans ; Monitoring, Immunologic ; Tomography, X-Ray Computed/methods ; Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/pathology ; Lung Neoplasms/pathology ; Multiple Pulmonary Nodules ; Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Tumor Microenvironment
    Language English
    Publishing date 2023-10-31
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-23-0128
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    Uh III Zs.135/5: Show issues Location:
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  7. Article ; Online: Single-molecule genome-wide mutation profiles of cell-free DNA for non-invasive detection of cancer.

    Bruhm, Daniel C / Mathios, Dimitrios / Foda, Zachariah H / Annapragada, Akshaya V / Medina, Jamie E / Adleff, Vilmos / Chiao, Elaine Jiayuee / Ferreira, Leonardo / Cristiano, Stephen / White, James R / Mazzilli, Sarah A / Billatos, Ehab / Spira, Avrum / Zaidi, Ali H / Mueller, Jeffrey / Kim, Amy K / Anagnostou, Valsamo / Phallen, Jillian / Scharpf, Robert B /
    Velculescu, Victor E

    Nature genetics

    2023  Volume 55, Issue 8, Page(s) 1301–1310

    Abstract: Somatic mutations are a hallmark of tumorigenesis and may be useful for non-invasive diagnosis of cancer. We analyzed whole-genome sequencing data from 2,511 individuals in the Pan-Cancer Analysis of Whole Genomes (PCAWG) study as well as 489 individuals ...

    Abstract Somatic mutations are a hallmark of tumorigenesis and may be useful for non-invasive diagnosis of cancer. We analyzed whole-genome sequencing data from 2,511 individuals in the Pan-Cancer Analysis of Whole Genomes (PCAWG) study as well as 489 individuals from four prospective cohorts and found distinct regional mutation type-specific frequencies in tissue and cell-free DNA from patients with cancer that were associated with replication timing and other chromatin features. A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected >90% of patients with lung cancer, including those with stage I and II disease. The fixed model was validated in an independent cohort, detected patients with cancer earlier than standard approaches and could be used to monitor response to therapy. This approach lays the groundwork for non-invasive cancer detection using genome-wide mutation features that may facilitate cancer screening and monitoring.
    MeSH term(s) Humans ; Cell-Free Nucleic Acids ; Prospective Studies ; Mutation ; Neoplasms/diagnosis ; Neoplasms/genetics ; Mutation Rate ; Lung Neoplasms/diagnosis ; Lung Neoplasms/genetics
    Chemical Substances Cell-Free Nucleic Acids
    Language English
    Publishing date 2023-07-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-023-01446-3
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  8. Article ; Online: Crystal ribcage: a platform for probing real-time lung function at cellular resolution.

    Banerji, Rohin / Grifno, Gabrielle N / Shi, Linzheng / Smolen, Dylan / LeBourdais, Rob / Muhvich, Johnathan / Eberman, Cate / Hiller, Bradley E / Lee, Jisu / Regan, Kathryn / Zheng, Siyi / Zhang, Sue / Jiang, John / Raslan, Ahmed A / Breda, Julia C / Pihl, Riley / Traber, Katrina / Mazzilli, Sarah / Ligresti, Giovanni /
    Mizgerd, Joseph P / Suki, Béla / Nia, Hadi T

    Nature methods

    2023  Volume 20, Issue 11, Page(s) 1790–1801

    Abstract: Understanding the dynamic pathogenesis and treatment response in pulmonary diseases requires probing the lung at cellular resolution in real time. Despite advances in intravital imaging, optical imaging of the lung during active respiration and ... ...

    Abstract Understanding the dynamic pathogenesis and treatment response in pulmonary diseases requires probing the lung at cellular resolution in real time. Despite advances in intravital imaging, optical imaging of the lung during active respiration and circulation has remained challenging. Here, we introduce the crystal ribcage: a transparent ribcage that allows multiscale optical imaging of the functioning lung from whole-organ to single-cell level. It enables the modulation of lung biophysics and immunity through intravascular, intrapulmonary, intraparenchymal and optogenetic interventions, and it preserves the three-dimensional architecture, air-liquid interface, cellular diversity and respiratory-circulatory functions of the lung. Utilizing these capabilities on murine models of pulmonary pathologies we probed remodeling of respiratory-circulatory functions at the single-alveolus and capillary levels during disease progression. The crystal ribcage and its broad applications presented here will facilitate further studies of nearly any pulmonary disease as well as lead to the identification of new targets for treatment strategies.
    MeSH term(s) Mice ; Animals ; Lung ; Rib Cage ; Intravital Microscopy
    Language English
    Publishing date 2023-09-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-023-02004-9
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  9. Article ; Online: Aberrant epithelial polarity cues drive the development of precancerous airway lesions.

    Tilston-Lunel, Andrew / Mazzilli, Sarah / Kingston, Nathan M / Szymaniak, Aleksander D / Hicks-Berthet, Julia / Kern, Joseph G / Abo, Kristine / Reid, Mary E / Perdomo, Catalina / Wilson, Andrew A / Spira, Avrum / Beane, Jennifer / Varelas, Xaralabos

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 18

    Abstract: Molecular events that drive the development of precancerous lesions in the bronchial epithelium, which are precursors of lung squamous cell carcinoma (LUSC), are poorly understood. We demonstrate that disruption of epithelial cellular polarity, via the ... ...

    Abstract Molecular events that drive the development of precancerous lesions in the bronchial epithelium, which are precursors of lung squamous cell carcinoma (LUSC), are poorly understood. We demonstrate that disruption of epithelial cellular polarity, via the conditional deletion of the apical determinant Crumbs3 (Crb3), initiates and sustains precancerous airway pathology. The loss of Crb3 in adult luminal airway epithelium promotes the uncontrolled activation of the transcriptional regulators YAP and TAZ, which stimulate intrinsic signals that promote epithelial cell plasticity and paracrine signals that induce basal-like cell growth. We show that aberrant polarity and YAP/TAZ-regulated gene expression associates with human bronchial precancer pathology and disease progression. Analyses of YAP/TAZ-regulated genes further identified the ERBB receptor ligand Neuregulin-1 (NRG1) as a key transcriptional target and therapeutic targeting of ERBB receptors as a means of preventing and treating precancerous cell growth. Our observations offer important molecular insight into the etiology of LUSC and provides directions for potential interception strategies of lung cancer.
    MeSH term(s) Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Cell Polarity/genetics ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Epithelium/metabolism ; Epithelium/pathology ; ErbB Receptors/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Membrane Glycoproteins/genetics ; Neuregulin-1/genetics ; Precancerous Conditions/genetics ; Precancerous Conditions/pathology ; Signal Transduction/genetics ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/genetics ; YAP-Signaling Proteins/genetics
    Chemical Substances Crb3 protein, mouse ; Membrane Glycoproteins ; Neuregulin-1 ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; YAP-Signaling Proteins ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2021-04-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2019282118
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  10. Article ; Online: Airway-Associated Macrophages in Homeostasis and Repair.

    Engler, Anna E / Ysasi, Alexandra B / Pihl, Riley M F / Villacorta-Martin, Carlos / Heston, Hailey M / Richardson, Hanne M K / Thapa, Bibek R / Moniz, Noah R / Belkina, Anna C / Mazzilli, Sarah A / Rock, Jason R

    Cell reports

    2020  Volume 33, Issue 13, Page(s) 108553

    Abstract: There is an increasing appreciation for the heterogeneity of myeloid lineages in the lung, but relatively little is known about populations specifically associated with the conducting airways. We use single-cell RNA sequencing, flow cytometry, and ... ...

    Abstract There is an increasing appreciation for the heterogeneity of myeloid lineages in the lung, but relatively little is known about populations specifically associated with the conducting airways. We use single-cell RNA sequencing, flow cytometry, and immunofluorescence to characterize myeloid cells of the mouse trachea during homeostasis and epithelial injury/repair. We identify submucosal macrophages, similar to lung interstitial macrophages, and intraepithelial macrophages. Following injury, there are early increases in neutrophils and submucosal macrophages, including M2-like macrophages. Intraepithelial macrophages are lost after injury and later restored by CCR2
    MeSH term(s) Animals ; Cells, Cultured ; Cytokines/metabolism ; Epithelial Cells/metabolism ; Epithelium/injuries ; Epithelium/metabolism ; Female ; Homeostasis ; Lung/metabolism ; Lung Injury/chemically induced ; Macrophages, Alveolar/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Animal ; Monocytes/metabolism ; Myeloid Cells/physiology ; Polidocanol ; Receptors, CCR2/genetics ; Receptors, CCR2/metabolism ; Regeneration ; Sequence Analysis, RNA ; Single-Cell Analysis ; Trachea/injuries ; Trachea/metabolism
    Chemical Substances Ccr2 protein, mouse ; Cytokines ; Receptors, CCR2 ; Polidocanol (0AWH8BFG9A)
    Language English
    Publishing date 2020-12-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2020.108553
    Database MEDical Literature Analysis and Retrieval System OnLINE

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