ArticleCell discovery2022
A bipotential organoid model of respiratory epithelium recapitulates high infectivity of SARS-CoV-2 Omicron variant.
Article in Cell discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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The trial behind it
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Who cites it
60 citing papers in PubMed, 77 citations in OpenAlex.
- Organoid-based evaluation of SA55 and Pemivibart against evolving SARS-CoV-2 variants.Emerging microbes & infections · 2026Article
- Endowing Flexibility of Alveolar Type II Cells to Recapitulate Development From Lung Bud to Alveoli.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Delayed antiviral immune response in alveolar type 2 cells increases susceptibility to influenza virus in alveoli.Chinese medical journal · 2026Article
- Pleura organoid transplantation facilitates visceral pleural repair through CD133Experimental & molecular medicine · 2026Article
- Extracellular matrix stiffness directs region-specific lung epithelial differentiation revealed by hPSC-derived lung organoids.Nature communications · 2026Article
- Cattle and human organoids reveal 2.3.4.4b H5N1 cross-species transmission potential and neuraminidase-specific neutralizing antibodies in humans.Nature communications · 2026Article
- New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026Review
- Organoids: From Bench to Bedside Applications.MedComm · 2026Review
- Respiratory Organ-on-a-Chip for Disease Modeling: From Architecture to Functional Integration.Advanced healthcare materials · 2026Review
- CRISPR-engineered human lung organoids with a biomolecular condensate reporter enable mechanistic toxicity monitoring.Materials today. Bio · 2026Article
- Lung organoids as a human system for Mycobacteria infection modeling and drug testing.The FEBS journal · 2026Review
- Exploring microorganism-host interactions: Emerging organoid models and analytical approaches.mLife · 2026Review
- Tropism, replication competence, and cellular responses of HAdV-14p1 in human airway organoids.iScience · 2026Article
- Modeling Alzheimer's disease with brain organoids: mechanisms, applications, and future directions.Frontiers in cell and developmental biology · 2026Review
- Engineering Organoid Platforms for Pathogenesis Research.Research (Washington, D.C.) · 2026Review
- Advancing the understanding of alveolar regeneration: Global research trends, thematic evolution, and emerging frontiers.Regenerative therapy · 2025Review
- Organoids in respiratory virus research: advances and perspectives.Molecular biomedicine · 2025Review
- Organoids: physiologically relevantJournal of virology · 2025Review
- Organoid-based neutralization assays reveal a distinctive profile of SARS-CoV-2 antibodies and recapitulate the real-world efficacy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Respiratory microphysiological system in respiratory research: recent advances and future prospects.Respiratory research · 2025Review
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
Abstract
The airways and alveoli of the human respiratory tract are lined by two distinct types of epithelium, which are the primary targets of respiratory viruses. We previously established long-term expanding human lung epithelial organoids from lung tissues and developed a 'proximal' differentiation protocol to generate mucociliary airway organoids. However, a respiratory organoid system with bipotential of the airway and alveolar differentiation remains elusive. Here we defined a 'distal' differentiation approach to generate alveolar organoids from the same source for the derivation of airway organoids. The alveolar organoids consisting of type I and type II alveolar epithelial cells (AT1 and AT2, respectively) functionally simulate the alveolar epithelium. AT2 cells maintained in lung organoids serve as progenitor cells from which alveolar organoids derive. Moreover, alveolar organoids sustain a productive SARS-CoV-2 infection, albeit a lower replicative fitness was observed compared to that in airway organoids. We further optimized 2-dimensional (2D) airway organoids. Upon differentiation under a slightly acidic pH, the 2D airway organoids exhibit enhanced viral replication, representing an optimal in vitro correlate of respiratory epithelium for modeling the high infectivity of SARS-CoV-2. Notably, the higher infectivity and replicative fitness of the Omicron variant than an ancestral strain were accurately recapitulated in these optimized airway organoids. In conclusion, we have established a bipotential organoid culture system able to reproducibly expand the entire human respiratory epithelium in vitro for modeling respiratory diseases, including COVID-19.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.