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

ABSTRACT: Human lungs contain unique cell populations in distal respiratory airways and terminal bronchioles (RA/TRB) that accumulate in patients with lung injury and idiopathic pulmonary fibrosis (IPF), a lethal lung disease. As these populations are absent in rodents, deeper understanding requires a human in vitro model. Here we convert human pluripotent stem cells into expandable spheres, called induced respiratory airway progenitors (iRAPs), consisting of ~99% RA/TRB-associated cell types. One hPSC can give rise to 1010 iRAP cells. We differentiate iRAPs through a stage consistent with transitional AT2 like cells into a population corresponding to mature AT1 cells with 95% purity. iRAPs with deletion of HPS1, which causes pulmonary fibrosis in humans, replicate the aberrant differentiation and recruitment of profibrotic fibroblasts observed in IPF, indicating that intrinsic dysfunction of RA/TRB-associated alveolar progenitors contributes to HPS1-related IPF. iRAPs may provide a system suitable for IPF drug discovery and validation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245722 | GEO | 2025/01/13

REPOSITORIES: GEO

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

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