Omics · study · 2026
Chromatin Landscape Analysis of Patient PDAC
Listed in NCBI GEO
We established a human pluripotent stem cell (hPSC)-derived pancreatic progenitor organoid (PO) culture that provides the cellular plasticity for PDAC modeling and supports robust gene editing.
Description
Through the combinatorial expression of oncogenic KRAS and deletion of multiple tumor suppressor genes (TSGs)，we successfully recapitulated the transcriptional hallmarks of initial malignant transformation and progression of PDAC in POs in vitro.
Moreover, these POs exhibited distinct histopathology from preneoplastic pancreatic intraepithelial neoplasia (PanIN) and moderately differentiated to poorly differentiated PDAC upon orthotopic transplantation. Further chromatin accessibility profiling unveiled 1) a progressive loss of pancreatic lineage program during disease development, accompanied by repression of TET1, 5hmc marking and hypermethylation of essential pancreatic lineage transcription factors and 2) an emergence of trans-lineage/malignant feature, associated with the opening of AP-1 motif enriched chromatin regions.
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Gene perturbation screening identified FOSL2, FOS, and JUNB as pro-malignancy AP-1 factors during malignant transformation of POs. Notably, inhibition of ERK, a regulator of AP-1, not only reversed AP-1 levels and malignant feature in transformed POs, but also derepressed TET1 and its associated chromatin regions. Thus, our de novo PDAC POs faithfully model the disease development and reveal distinct but concerted mechanisms that drive the cellular plasticity in PDAC.
The comprehensive validation of this model against clinical datasets approves its potential for discovery of therapeutic targets and biomarkers for preventive screening in the future.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE272nnn/GSE272463 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272463 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1136913 ncbi.nlm.nih.gov/bioproject/PRJNA1136913 ↗
project · from NCBI GEO
- PubMed 42161274 pubmed.ncbi.nlm.nih.gov/42161274 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE272463 | 10 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |