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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 17, 2024 |
| Title |
ROR2 regulates cellular plasticity in pancreatic neoplasia and adenocarcinoma (snATAC-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells to precancerous lesions to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We found that normal acinar cell differentiation, maintained by the transcription factor Pdx1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in mouse and human. We have identified the receptor tyrosine kinase Ror2 as marker of a gastric metaplasia (SPEM)-like identity in the pancreas. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to carcinoma. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial to mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition.
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| Overall design |
Nuclei were isolated from frozen tissue of Ptf1aERT, Ptf1aERT;K*, Ptf1aERT;Pdx1f/f and Ptf1aERT;K*;Pdx1f/f mice, 2 and 10 weeks after Tamoxifen-induced CreERT recombination (n=2). Nuclei were analyzed using snATACseq.
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| Contributor(s) |
Benitz S, Steep A, Loveless I, Crawford H |
| Citation(s) |
38975886 |
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| Submission date |
Jan 18, 2024 |
| Last update date |
Oct 29, 2024 |
| Contact name |
Simone Benitz |
| Organization name |
Henry Ford Health System
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| Street address |
2799 W Grand Blvd
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| City |
Detroit |
| ZIP/Postal code |
48202 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| GSM8023960 |
Ptf1aERT;K*, 2 weeks, replicate 2 |
| GSM8023961 |
Ptf1aERT;Pdx1f/f, 2 weeks, replicate 1 |
| GSM8023962 |
Ptf1aERT;Pdx1f/f, 2 weeks, replicate 2 |
| GSM8023963 |
Ptf1aERT;K*;Pdx1f/f, 2 weeks, replicate 1 |
| GSM8023964 |
Ptf1aERT;K*;Pdx1f/f, 2 weeks, replicate 2 |
| GSM8023965 |
Ptf1aERT;K*, 10 weeks, replicate 1 |
| GSM8023966 |
Ptf1aERT;K*, 10 weeks, replicate 2 |
| GSM8023967 |
Ptf1aERT;K*;Pdx1f/f, 10 weeks, replicate 1 |
| GSM8023968 |
Ptf1aERT;K*;Pdx1f/f, 10 weeks, replicate 2 |
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| This SubSeries is part of SuperSeries: |
| GSE253600 |
ROR2 regulates cellular plasticity in pancreatic neoplasia and adenocarcinoma |
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| Relations |
| BioProject |
PRJNA1066337 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE253597_RAW.tar |
21.4 Gb |
(http)(custom) |
TAR (of BED, CSV, TBI, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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