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- W2989988788 abstract "While the pathophysiology remains unclear, growing evidence suggests that a pro-fibrotic milieu and dysfunctional epithelial repair likely play key roles in IPF. An emergence of airway epithelial like cells of unknown origin is frequently observed in distorted alveolar regions in IFP. We aimed to investigate if a pro-fibrotic environment could drive aberrant trans-differentiation of alveolar epithelial progenitors towards airway epithelial like cells. We used an iPSC-derived air-liquid interface model of directed ATII cell differentiation and treated the cells with an IPF-relevant cocktail (IPF-RC), composed of cytokines previously described to be upregulated in IPF patient lungs. Characterization by qRT-PCR, RNAseq, IF and TEM confirmed the ATII-like phenotype of the cultures. IPF-RC stimulation during differentiation resulted in significantly reduced expression of SFTPC and increased airway related transcript expression, including KRT5, SCGB1A1, MUC5B and BPIFB1. In comparison, primary small airway basal cells differentiated in the presence of IPF-RC displayed an upregulated expression of KRT5, BPIFB1 and MUC5AC (but not MUC5B), and a downregulation in SCGB1A1. We have thus shown that an IPF-related cytokine environment has the potential to drive aberrant alveolar epithelial progenitor differentiation towards an airway epithelial like expression signature, resembling that observed in IPF lungs, that could be distinguished from primary small airway basal cells differentiated in the presence of the same cytokines. These findings indicate that aberrant alveolar epithelial stem cell differentiation could play a role in IPF-associated bronchiolisation." @default.
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- W2989988788 date "2019-09-28" @default.
- W2989988788 modified "2023-09-26" @default.
- W2989988788 title "IPF-relevant cytokine cocktail induced changes in iPSC-derived alveolar epithelial and primary airway basal cell differentiation" @default.
- W2989988788 doi "https://doi.org/10.1183/13993003.congress-2019.oa1902" @default.
- W2989988788 hasPublicationYear "2019" @default.
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