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

UID: 11009

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 chromatin accessibility (scATAC-seq) profiles of lineage-traced pancreatic epithelial cells (mKate2+) freshly-isolated by FACS-sorting from benign neoplasia (K3) or malignant (K5) pancreatic tissues: To characterize benign neoplasia (K3), KC;RIK (Ptf1a-Cre;RIK;LSLKrasG12D) mice were treated with caerulein at 5 weeks of age, and mKate2+ cells were subjected to scATAC-seq analyses 3 weeks thereafter. To characterize invasive disease (K5), pancreatic ductal adenocarcinoma (PDAC) cells were isolated from cancer lesions arising in autochthonous transgenic models (KPC;RIK (Ptf1a-Cre;RIK;LSL-KrasG12D;p53fl/+). Data from additional pre-malignant stages (K1, K2) were extracted from GSE137069, from KC-RIK mice treated with caerulein or PBS at 5 weeks of age, and analyzed 2 days thereafter. 2 biological replicates (independent mice) were used per experimental condition."
Subject of Study
Mus musculus
Subject(s)
Adenocarcinoma
Carcinogenesis
Carcinoma, Pancreatic Ductal
Cell Plasticity
Chromatin Immunoprecipitation Sequencing
Pancreatic Neoplasms
OncoTree Cancer Type(s)
Pancreatic Adenocarcinoma
Access via GEO


Accession #: GSE207698

Access via BioProject


Accession #: PRJNA856703

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 NovaSeq 6000
Dataset Format(s)
TAR, TXT, H5, H5AD
Dataset Size
598.6 MB (H5AD), 380.9 MB (TAR), 802 B (TXT)
Data Catalog Record Updated
2023-11-07