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July 24, 2026American Journal of Respiratory Cell and Molecular Biology

Emergence of Disease-relevant Aberrant Epithelial Cell States in Human Alveolar Organoids

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Authors

HDHolly E. DavidADA. DietrichCCCarla L. Calvi

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Overview

Randomized trial investigates aberrant epithelial cell states in alveolar organoids, suggesting HIF2's crucial role in pulmonary fibrosis.

Key Points

  • The central aim is to explore how HIF2 activation affects alveolar epithelial cell behavior and states in a lab model.
  • Utilized primary human alveolar epithelial organoids expanded from donor lungs.
  • Examined organoids' responses to alveolar differentiation media (ADM) and pharmacologic modulators for biased HIF signaling.
  • Conducted multimodal analyses including scRNA-seq, quantitative label-free proteomics, and Cell Painting.
  • ADM induced expression of AT1 markers but did not produce mature AT1-like cells, leading to KRT17+/KRT5- aberrant basaloid-like cells (p = 3x10−286).
  • HIF2 activation intensified the transitions towards aberrant states in the organoids.
  • Gene and protein analyses indicated shifts in cytoskeletal structures and metabolic pathways linked to the aberrant markers.

Cite This Study

David et al. (2026) studied this question.

synapsesocial.com/papers/6a6301a6395161722cd16399https://doi.org/10.1093/ajrcmb/aanag150
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