Regulation of immune responses by the airway epithelial cell landscape

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(6), P. 347 - 362

Published: Jan. 13, 2021

Language: Английский

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An integrated cell atlas of the lung in health and disease

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(6), P. 1563 - 1577

Published: June 1, 2023

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations individual the variability present in population. Here we integrated Human Lung Cell Atlas (HLCA), combining 49 respiratory system into single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents consensus re-annotation with matching marker genes, including annotations rare previously undescribed types. Leveraging diversity individuals HLCA, identify gene modules that are associated demographic covariates such as age, sex body mass index, well changing expression along proximal-to-distal axis bronchial tree. Mapping new data to enables rapid annotation interpretation. Using reference for study disease, shared states across multiple lung diseases, SPP1

Language: Английский

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Senescence of Alveolar Type 2 Cells Drives Progressive Pulmonary Fibrosis

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2020, Volume and Issue: 203(6), P. 707 - 717

Published: Sept. 29, 2020

Rationale: Idiopathic pulmonary fibrosis (IPF) is an insidious and fatal interstitial lung disease associated with declining function. Accelerated aging, loss of epithelial progenitor cell function and/or numbers, cellular senescence are implicated in the pathogenies IPF. Objectives: We sought to investigate role alveolar type 2 (AT2) initiation progression therapeutic potential targeting senescence-related pathways senescent cells. Methods: Epithelial cells 9 control donor proximal distal tissues 11 IPF fibrotic were profiled by single-cell RNA sequencing assesses contribution fraction for A novel mouse model conditional AT2 was generated study fibrosis. Measurements Main Results: show that isolated from tissue exhibit characteristic transcriptomic features senescence. used Sin3a adult initiate a program p53-dependent senescence, depletion, spontaneous, progressive establish rather than promotes either genetic or pharmacologic interventions p53 activation block fibrogenesis. Conclusions: Senescence sufficient drive Early attenuation elimination promising approaches prevent

Language: Английский

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Human Lung Stem Cell-Based Alveolospheres Provide Insights into SARS-CoV-2-Mediated Interferon Responses and Pneumocyte Dysfunction

Cell stem cell, Journal Year: 2020, Volume and Issue: 27(6), P. 890 - 904.e8

Published: Oct. 21, 2020

Language: Английский

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SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response

Cell stem cell, Journal Year: 2020, Volume and Issue: 27(6), P. 962 - 973.e7

Published: Sept. 18, 2020

Language: Английский

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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(3), P. 546 - 559

Published: March 1, 2021

Language: Английский

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Lung transplantation for patients with severe COVID-19

Science Translational Medicine, Journal Year: 2020, Volume and Issue: 12(574)

Published: Dec. 1, 2020

Some patients with severe COVID-19 develop end-stage pulmonary fibrosis for which lung transplantation may be the only treatment.

Language: Английский

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Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung

Circulation, Journal Year: 2021, Volume and Issue: 144(4), P. 286 - 302

Published: May 25, 2021

Cellular diversity of the lung endothelium has not been systematically characterized in humans. We provide a reference atlas human endothelial cells (ECs) to facilitate better understanding phenotypic and composition comprising endothelium.We reprocessed control single-cell RNA sequencing (scRNAseq) data from 6 datasets. EC populations were through iterative clustering with subsequent differential expression analysis. Marker genes validated by fluorescent microscopy situ hybridization. scRNAseq primary ECs cultured vitro was performed. The signaling network between different cell types studied. For cross-species analysis or disease relevance, we applied same methods obtained mouse lungs pulmonary hypertension.Six datasets reanalyzed annotated identify >15 000 vascular 73 individuals. Differential revealed signatures corresponding lineage, including panendothelial, panvascular, subpopulation-specific marker gene sets. Beyond broad cellular categories lymphatic, capillary, arterial, venous ECs, found previously indistinguishable subpopulations; among EC, identified 2 populations: pulmonary-venous (COL15A1neg) localized parenchyma systemic-venous (COL15A1pos) airways visceral pleura; capillary confirmed their subclassification into recently discovered aerocytes EDNRB, SOSTDC1, TBX2 general EC. that all types, aerocytes, are present mice conserved humans mice. Ligand-receptor connectome important homeostatic crosstalk other resident types. commercially available demonstrated loss native phenotype culture. is maintained hypertension. Our article accompanied an online mining tool (www.LungEndothelialCellAtlas.com).Our integrated provides comprehensive well-crafted normal confirms describes detail unrecognized across large number

Language: Английский

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Interstitial lung diseases

The Lancet, Journal Year: 2022, Volume and Issue: 400(10354), P. 769 - 786

Published: Aug. 11, 2022

Language: Английский

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The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Jan. 3, 2022

Abstract The SARS-CoV-2 Omicron/BA.1 lineage emerged in late 2021 and rapidly displaced the Delta variant before being overtaken itself globally by, Omicron/BA.2 early 2022. Here, we describe how Omicron BA.1 BA.2 show a lower severity phenotype hamster model of pathogenicity which maps specifically to spike gene. We further that is attenuated lung cell line but replicates more rapidly, albeit peak titres, human primary nasal cells. This replication also (including emerging BA.4) shows fusogenicity preference for entry via endosomal route. map altered route partially S2 domain, particularly substitution N969K. Finally, pseudovirus with spike, engineered domain confer Delta-like retains antigenic properties Omicron. distinct separation between genetic determinants these two key phenotypes, raising concerning possibility future variants large distance from currently circulating vaccine strains will not necessarily display intrinsic seen during infection.

Language: Английский

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