A Human Immuno‐Lung Organoid Model to Study Macrophage‐Mediated Lung Cell Senescence Upon SARS‐CoV‐2 Infection
Source abstract
Abstract
Abstract While COVID‐19 affects multiple organ systems, the human respiratory system is the primary viral target and main site for disease progression. In this study, spatial transcriptional assays (NanoString CosMx) are utilized to analyze both explant and autopsy samples from non‐COVID and COVID‐19 lungs, identifying the activation of proinflammatory macrophages in COVID‐19 explants. It is further developed immuno‐lung organoids comprising hPSC‐derived alveolar and airway organoids co‐cultured with macrophages to investigate the impact and underlying mechanisms of macrophage‐mediated lung damage following SARS‐CoV‐2 infection. The findings demonstrate that proinflammatory macrophages induce lung cell senescence through the THBS1–(ITGA3+ITGB1) signaling axis, a mechanism further validated using spatial transcriptomics. This study not only establishes physiologically relevant immuno‐lung organoid models for modeling macrophage‐mediated tissue damage, but also identifies a previous unrecognized role of the THBS1‐(ITGA3+ITGB1) pathway in driving lung cell senescence during infectious disease.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Single-cell and spatial transcriptomics · Immune responses and vaccinations · Immune cells in cancer
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Surgery Weill Cornell Medicine 1300 York Ave New York NY 10065 USA
Center for Genomic Health Weill Cornell Medicine 1300 York Ave New York NY 10065 USA
Genomic Resource Core Facility Weill Cornell Medicine New York NY 10065 USA
Columbia Center for Human Development and Division of Digestive and Liver Disease Department of Medicine, Vagelos College of Physicians and Surgeons Columbia University IrvingMedical Center New York NY 10032 USA
Aaron Diamond AIDS Research Center Columbia University Vagelos College of Physicians and Surgeons New York NY 10032 USA
Gilbert S. Omenn Department of Computational Medicine & Bioinformatics University of Michigan Ann Arbor MI 48109 USA
Department of Pathology and Cell Biology Columbia University Irving Medical Center New York NY 10032 USA
Funding
National Heart, Lung, and Blood Institute · U.S. Department of Defense
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