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Omics · study · 2026

Stromal TNF–NFκB signaling impairs acinar differentiation through inflammation-driven epithelial–stromal crosstalk in chimeric salivary gland organoids

Listed in NCBI GEO

Salivary gland organoids enable long-term epithelial expansion but lack stromal compartments that regulate glandular differentiation in vivo.

Description

Here, we developed chimeric salivary gland organoids (cSGOs) by layering embryonic day 13 stromal cells over postnatal day 1 epithelial organoids. cSGOs incorporated fibroblasts, immune cells, endothelial cells, and neuronal populations while preserving acino-ductal architecture.

Single-cell RNA sequencing revealed that stromal fibroblasts supply FGF ligands supporting epithelial proliferation, yet acinar differentiation remained stalled. Pseudotime and pathway analyses identified TNF-NFκB signaling from stromal immune cells as selectively enriched in proacinar cells. Dexamethasone suppressed this inflammatory axis, expanded the proacinar population, and restored acinar marker expression.

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Direct NFκB inhibition with BAY11-7082 phenocopied the glucocorticoid effect, implicating epithelial NFκB as a stromal-derived inflammatory checkpoint limiting acinar maturation. These findings support a mechanistic link between stromal inflammation and impaired acinar differentiation and identify a candidate signaling node for therapeutic intervention.

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Life Sciences
Inferred from text
RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 10 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE32617211 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
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[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:single-cell-rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
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