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Series GSE253597 Query DataSets for GSE253597
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
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.
 
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.
 
Contributor(s) Benitz S, Steep A, Loveless I, Crawford H
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Jan 18, 2024
Last update date Jun 18, 2024
Contact name Simone Benitz
Organization name Henry Ford Health System
Street address 2799 W Grand Blvd
City Detroit
ZIP/Postal code 48202
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM8023957 Ptf1aERT, 2 weeks, replicate 1
GSM8023958 Ptf1aERT, 2 weeks, replicate 2
GSM8023959 Ptf1aERT;K*, 2 weeks, replicate 1
This SubSeries is part of SuperSeries:
GSE253600 ROR2 regulates cellular plasticity in pancreatic neoplasia and adenocarcinoma
Relations
BioProject PRJNA1066337

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Supplementary file Size Download File type/resource
GSE253597_RAW.tar 21.4 Gb (http)(custom) TAR (of BED, CSV, TBI, TSV)
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Raw data are available in SRA
Processed data provided as supplementary file

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