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| Status |
Public on Mar 14, 2017 |
| Title |
Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring oncogenic KRAS and induced mutations in CDKN2A, SMAD4 and TP53 expand in vitro as epithelial spheres. After pancreatic transplantation, mutant clones form lesions histologically similar to native PanINs, including prominent stromal responses. Gene expression profiling reveals molecular similarities of mutant clones with native PanINs, and identifies potential PanIN biomarker candidates including Neuromedin U, a circulating peptide hormone. Prospective reconstitution of human PanIN development from primary cells provides experimental opportunities to investigate pancreas cancer development, progression and early-stage detection.
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| Overall design |
We performed RNAseq analysis using KCT, KCST, KECST clones along with donor-matched control ductal sphere cells (S1-CTRL, S1 KCSTclone3, S1 KECSTclone3, S1 KCSTclone4, S1 KECSTclone4, S2 KCTclone3, S2 KCSTclone8, S2 KECSTclone8).
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| Contributor(s) |
Lee J, Kim SK |
| Citation(s) |
28272465 |
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| Submission date |
Oct 20, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Jonghyeob Lee |
| Organization name |
Stanford University School of Medicine
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| Street address |
279 Campus Drive, Beckman Center B300
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA349475 |
| SRA |
SRP091873 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE88997_Lee-Total-Raw-Count.txt.gz |
696.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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