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Epigenetic plasticity cooperates with emergent cell-cell interactions to drive neoplastic tissue remodeling in the pancreas [scRNA-seq]

UID: 11011

Author(s): Burdziak, Cassandra*, Alonso-Curbelo, Direna*, Pe'er, Dana*, Lowe, Scott W.* * MSK affiliated

Description
Summary from GEO:

"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."

Overall design from GEO:

"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 possible, 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."
Subject of Study
Mus musculus
Subject(s)
Adenocarcinoma
Carcinogenesis
Carcinoma, Pancreatic Ductal
Cell Plasticity
Pancreatic Neoplasms
RNA-Seq
Access via GEO


Accession #: GSE207938

Access via BioProject


Accession #: PRJNA857716

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus and BioProject databases provide open access to these files.
Associated Publications
Burdziak C, Alonso-Curbelo D, Walle T, Reyes J, Barriga F, Haviv D, Xie Y, Zhao Z, Zhao C, Chen H, Chaudhary O, Masilionis I, Choo Z, Gao V, Luan W, Wuest A, Ho Y, Wei Y, Quail D, Koche R, Mazutis L, Chaligné R, Nawy T, Lowe S, Pe'er D. Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis. Science. 2023; 380(6645):eadd5327.
Equipment Used
Illumina HiSeq 2500

High throughput sequencing system

Illumina NovaSeq 6000
Dataset Format(s)
CSV, TAR, MTX, TXT, H5AD
Dataset Size
931.8 MB (3 H5AD files), 2.4 GB (TAR), 2.2 KB (TXT)
Data Catalog Record Updated
2023-11-07