An epigenetic program established by gene – environment interactions initiates pancreatic carcinogenesis [scATAC-Seq]
UID: 10943
- Description
- Summary from GEO:
"Damaged tissues have increased risk of cancer development through poorly understood mechanisms. For example, in the pancreas, tissue damage collaborates with activating mutations in the Kras oncogene to dramatically accelerate the formation of early neoplastic lesions and, ultimately, pancreatic cancer. By integrating genomics, single-cell chromatin assays and spatiotemporally-controlled functional perturbations in autochthonous tumor models, we show that the combination of Kras mutation and tissue damage promotes a functionally relevant chromatin state in the pancreatic epithelium that distinguishes neoplastic transformation from normal regeneration and is inherited throughout malignant evolution. This cancer-associated epigenetic state emerges remarkably fast, involves chromatin accessibility changes not induced by pancreatic injury alone, and contributes to the early activation of neoplasia specific genes that define advanced human pancreatic cancer. Among the genes activated by injury-facilitated chromatin reprogramming are a series of known and novel cancer-related factors, including the alarmin cytokine IL33, which cooperates with mutant Kras in driving neoplastic transformation in the absence of tissue damage. Collectively, our study demonstrates how gene-environment interactions can rapidly produce gene regulatory programs that dictate early neoplastic commitment and provides a molecular framework for understanding the cooperation between genetics and environmental cues in cancer initiation."
Overall design from GEO:
"Characterization of single-cell chromatin accessibility profiles of lineage-traced pancreatic epithelial cells isolated directly by FACS-sorting (mKate2+) from early neoplastic pancreatic tissues: To assess the effects of tissue injury in mutant Kras-expressing pancreata, lineage-traced (mKate2+) pancreatic epithelial cells were sorted from KC;RIK (p48-Cre;RIK;LSLKrasG12D) littermate male mice treated with caerulein or PBS (vehicle control) at 5 weeks of age."
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Access via GEO
Accession #: GSE137069Access via BioProject
Accession #: PRJNA564503Access via SRA
Accession #: SRP220999 - Access Restrictions
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Free to All
- Access Instructions
- The NCBI Gene Expression Omnibus, SRA and BioProject databases provide open access to these files.
- Associated Publications
- Equipment Used
- Dataset Format(s)
- CSV, TAR, H5
- Dataset Size
- 130.1 MB (H5), 172 MB (TAR), 7.2 GB (CSV)
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