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Generation of expandable multipotential distal lung progenitors from human pluripotent stem cells that model idiopathic pulmonary fibrosis [bulk RNA-Seq]

GSE245721 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/01/09 Platform GPL24676
Summary
Human lungs contain distal respiratory airways (RAs) that are absent in rodents and contain unique cell populations that are more abundant in patients with lung injury and idiopathic pulmonary fibrosis (IPF). A deeper understanding of the potential of these cells requires an in vitro model. Here we report the generation from human pluripotent stem cells of expandable spheres (‘induced respiratory airway progenitors’ (iRAPs)) consisting of RA-associated cell types that could be differentiated into type 1 and type 2 alveolar epithelial cells in defined conditions and show defects that are hallmarks of IPF when mutant for HPS1, a gene associated with IPF in humans. These data indicate that alveolar epithelial cells can derive from distal airway progenitors and that their intrinsic dysfunction may be involved in aberrant, fibrotic repair in IPF. iRAPs thus provide a model to gain insight into human lung regeneration and into pathogenesis of IPF.
Published in
Human respiratory airway progenitors derived from pluripotent cells generate alveolar epithelial cells and model pulmonary fibrosis
Pezet MG, Torres JA, Thimraj TA et al. · Nature biotechnology 2026 · PMID 39994483 · doi:10.1038/s41587-025-02569-0
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Direct links to NCBI, no account and no request form: the whole study as GSE245721_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1029623 and SRA study SRP467161. Searching any of these in the dataset finder brings you back here.

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