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Omics · study · 2026

AP-1 mediated chromatin changes govern alveolar type 2 cell transition in lung injury-repair [multiome]

Listed in NCBI GEO

Facultative stem cells including alveolar type 2 (AT2) cells in the lung must toggle between unipotent specialization and multipotent plasticity during injury-repair.

Description

The underlying molecular switches and epigenetic changes remain unclear yet dictate regeneration versus pathology. Using multiomics and mouse genetics, we show that AP-1 members FOS, FOSB, and JUNB promote an injury-induced transitional AT2 cell state and associated chromatin landscape.

Joint transcriptomic-epigenomic profiling and immunostaining distinguish CLDN4+ AT2 cells as a KRT8high subset with open chromatin highly enriched for AP-1 motifs. JUNB and FOSB accumulate in these cells upon viral injury and, along with constitutive FOS, are required for CLDN4 induction, AT2 cell dispersion, and senescence signaling toward fibroblasts, while impacting region-specific alveolar type 1 (AT1) differentiation.

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AP-1 activation also occurs in mouse AT2 cells expressing oncogenic Kras and transitional cells of human lung adenocarcinoma. Our work refines AT2 transitional states and reveals a gene regulatory logic shared by tissue repair and tumorigenesis.

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Life Sciences
Inferred from text
Genetics 69%
Provenance · 1 source records, 9 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE31053914 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].anzsrc:group:3105enrichment · NCBI GEOtaxonomy-embedding@1.1.0title+keywords+description (69%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title