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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 27, 2023 |
| Title |
Epigenetic plasticity cooperates with emergent cell-cell interactions to drive neoplastic tissue remodeling in the pancreas [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In pancreatic cancer, select cells within a homogeneous epithelium drive tumorigenesis in response to an environmental trigger, suggesting key uncharacterized roles for epigenetics and cellular context. To investigate epigenetic plasticity in early tumorigenesis, we performed single-cell transcriptional and chromatin accessibility sequencing of Kras-mutant pancreatic cancer models, encompassing initiation to malignant stages and wild-type tissue. Our analysis identifies a few progenitor states that correspond to known cells-of-origin, exhibit the greatest measured epigenetic plasticity, and are primed for diverse neoplastic fates. Plasticity is strongly associated with accessibility near receptor and ligand loci. We delineated robust communication modules and a feedback loop between IL33-expressing epithelial and immune cells with broad tissue impacts, which we confirmed by genetic perturbation in mice. Our results promise to nominate early interception strategies for this lethal cancer.
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| Overall design |
Characterization of single-cell transcriptional profiles of lineage-traced pancreatic epithelial cells (mKate2+) isolated directly by FACS-sorting from normal (N1), regenerating (N2), pre-neoplastic (K1, K2), bening neoplastic (PanIN, K3, K4), malignant (PDAC, K5) and metastasis (K6) murine pancreatic tissues: To assess the effects of injury-induced inflammation on mutant Kras-expressing or Kras wild-type pancreatic epithelia, cells were sorted from KC;RIK (p48-Cre;RIK;LSLKrasG12D) or C;RIK (p48-Cre;RIK) male mice treated with caerulein or PBS (vehicle control) at 5 weeks of age, using littermates when possibe, and were analyzed 2 o 21 days thereafter. To characterize invasive disease, pancreatic ductal adenocarcinoma (PDAC) cells were isolated from cancer lesions arising in autochthonous transgenic models (KPC;RIK (p48Cre;RIK;LSL-KrasG12D;p53fl/+ or p48Cre;RIK;LSL-KrasG12D;p53R127H/+). 2-3 biological replicates (independent mice) were used per experimental condition.
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| Contributor(s) |
Burdziak C, Alonso-Curbelo D, Pe'er D, Lowe SW |
| Citation(s) |
37167403 |
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| Submission date |
Jul 11, 2022 |
| Last update date |
Jun 02, 2023 |
| Contact name |
Cassandra Burdziak |
| E-mail(s) |
burdziac@mskcc.org
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| Organization name |
Memorial Sloan Kettering Cancer Center
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| Street address |
417 E 68th St
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| City |
New York City |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (49)
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| This SubSeries is part of SuperSeries: |
| GSE207943 |
Epigenetic plasticity cooperates with emergent cell-cell interactions to drive neoplastic tissue remodeling in the pancreas |
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| Relations |
| BioProject |
PRJNA857716 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE207938_Combined_ImmuneEpi.h5ad.gz |
171.5 Mb |
(ftp)(http) |
H5AD |
| GSE207938_PerturbationCohort_K3.h5ad.gz |
47.5 Mb |
(ftp)(http) |
H5AD |
| GSE207938_ProgressionCohort.h5ad.gz |
712.8 Mb |
(ftp)(http) |
H5AD |
| GSE207938_RAW.tar |
2.4 Gb |
(http)(custom) |
TAR (of CSV, MTX) |
| GSE207938_README_scRNA.txt |
2.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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