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Early cell autonomous and niche-mediated alveolar epithelial response to influenza infection in primary lung organoids

GSE327614 Homo sapiens; Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 24 samples Submitted 2026/04/10 Platform GPL24676Platform GPL24247
Summary
Influenza A virus (IAV) infection is a significant cause of morbidity and mortality for patients worldwide. Alveolar type 2 (AT2) cells are the preferential target of IAV as part of the pathogenesis of viral pneumonia and acute respiratory distress syndrome (ARDS). Early IAV infection of alveolar cells has been challenging to model both in vitro and in vivo. To address this challenge, we used a combination of murine and human primary alveolar organoids to define methods for robust IAV infection and evaluated cell-autonomous consequences of IAV using a temporal series of multiome paired single nuclei RNA/ATAC sequencing. Infected AT2 cells undergo conserved changes defined by early loss of surfactant secretion, decreased lipid biogenesis, a rapid burst of antiviral response, and late viral-mediated suppression. Surprisingly, uninfected AT2 cells undergo substantial transcriptional and epigenomic changes in IAV-treated cultures, leading to transition to damage-associated cell states within hours via a process driven by the inflammatory milieu of murine organoids. Together, these data provide new methods for high-fidelity modeling of IAV infection in alveolar cells and define a conserved AT2 cell response signature to IAV with implications for ARDS pathogenesis.
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Direct links to NCBI, no account and no request form: the whole study as GSE327614_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 24 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1451530 and SRA study SRP690828. Searching any of these in the dataset finder brings you back here.

Study design
24 conditions, each sampled once — no replicated groups

Read from 24 sample titles: 24 distinct titles with little repetition. Check it against the sample list below before relying on it.

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