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Omics · study · 2026

Jag1-regulated hybrid-EMT state identifies a subset of CD9hi pancreatic tumour-initiating cells with enriched stemness

Listed in NCBI GEO

We previously identified a pancreatic ductal adenocarcinoma (PDAC) subpopulation capable of initiating PDAC and giving rise to PDAC heterogeneity, marked by the tetraspanin CD91.

Description

PDAC shows great cellular heterogeneity, with pronounced epithelial and mesenchymal cancer cell populations, and it has been suggested that cancer cells with hybrid epithelial-mesenchymal transition (EMT) features peculiarly contribute to tumour aggressiveness2,3.

Here, we identify a stable hybrid-EMT subpopulation that are highly enriched for tumour initiating cell (TIC) properties which constituted a subpopulation of CD9hi TICs1. Hybrid-EMT CD9hi TICs showed increased capacity to form organoids and generate epithelial and mesenchymal tumour cell progeny. Interestingly, in contrast to the majority of PDAC organoids with cystic morphology, hybrid-EMT organoids exhibited a solid morphology and were able to give rise to both cystic and filled organoids, implying a relationship between stemness and solid morphology.

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Cell depletion of hybrid-EMT cells led to gradual collapse of organoids formation capability, suggesting hybrid-EMT cells are required for long-term organoid formation. Mechanistically, hybrid-EMT cells upregulated Jag1, which promoted their self-renewal by activating the Notch signalling pathway. Thus, the hybrid EMT state is a defining feature of stem cells in PDAC.

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From keywords
Life Sciences
Inferred from text
Cancer 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE24573613 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
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[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