Pulmonary organoid models demonstrate compositionally driven epithelial plasticity and immune polarization

iScience 2026 Open access

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Authors: Sophie E. Edelstein, Satoshi Mizoguchi, Maria Tomàs Gracia, Nuoya Wang, VI Lee, Tomohiro Obata, Hahram Kim, Connor Haynes, Colten Danelski, Tomoshi Tsuchiya, Maor Sauler, Micha Sam Brickman Raredon
DOI: 10.1016/j.isci.2026.115030
Cited by: 1
References: 147

Abstract

stressed progenitors, RAS-like intermediates, and hillock-like cells, alongside macrophage activation profiles. In mesenchyme-rich contexts, epithelial-immune-mesenchymal crosstalk reinforced inflammatory signaling and stabilized transitional cells, while immune-dominant inputs favored ATI-like repair and squamous remodeling. Hillock-like cells displayed context-dependent activation and expressed immune-regulatory genes, suggesting a role as epithelial orchestrators calibrating inflammatory response during regeneration. Regenerative outcomes were associated with multicellular signaling networks integrating stress sensing, immune coordination, and epithelial resilience. This platform facilitates modeling of milieu-specific regenerative mechanisms and informs strategies to redirect epithelial fate in chronic lung disease.

Fields of Study & Subjects

Cancer Cells and Metastasis Immune cells in cancer Cellular Mechanics and Interactions

Publication details

Journal / source
iScience
Publisher
Elsevier BV
Volume
29
Issue
4
Pages
115030–115030
Publication date
24 February 2026
Language
EN