Single-Cell Analysis Differentiates the Effects of p53 Mutation and p53 Loss on Cell Compositions of Oncogenic Kras-Driven Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignant disease with a dismal prognosis. In the past decades, a plethora of genetically engineered mouse models (GEMMs) with autochthonous pancreatic tumor development have greatly facilitated studies of pancreatic cancer. Commonly used GEMM...
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MDPI AG
2023-11-01
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| author | Xinlei Sun Daowei Yang Yang Chen |
| author_facet | Xinlei Sun Daowei Yang Yang Chen |
| author_sort | Xinlei Sun |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignant disease with a dismal prognosis. In the past decades, a plethora of genetically engineered mouse models (GEMMs) with autochthonous pancreatic tumor development have greatly facilitated studies of pancreatic cancer. Commonly used GEMMs of PDAC often harbor the oncogenic KRAS driver mutation (<i>Kras<sup>G12D</sup></i>), in combination with either p53 mutation by knock-in strategy (<i>Trp53<sup>R172H</sup></i>) or p53 loss by conditional knockout (<i>Trp53<sup>cKO</sup></i>) strategy, in pancreatic cell lineages. However, the systematic comparison of the tumor microenvironment between <i>Kras<sup>G12D</sup></i>; <i>Trp53<sup>R172H</sup></i> (KP<sup>mut</sup>) mouse models and <i>Kras<sup>G12D</sup></i>; <i>Trp53<sup>cKO</sup></i> (KP<sup>loss</sup>) mouse models is still lacking. In this study, we conducted cross-dataset single-cell RNA-sequencing (scRNA-seq) analyses to compare the pancreatic tumor microenvironment from KP<sup>mut</sup> mouse models and KP<sup>loss</sup> mouse models, especially focusing on the cell compositions and transcriptomic phenotypes of major cell types including cancer cells, B cells, T cells, granulocytes, myeloid cells, cancer-associated fibroblasts, and endothelial cells. We identified the similarities and differences between KP<sup>mut</sup> and KP<sup>loss</sup> mouse models, revealing the effects of p53 mutation and p53 loss on oncogenic KRAS-driven pancreatic tumor progression. |
| first_indexed | 2024-03-09T16:55:32Z |
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| id | doaj.art-3673c9519ae34f6c999a2d7404c820da |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T16:55:32Z |
| publishDate | 2023-11-01 |
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| series | Cells |
| spelling | doaj.art-3673c9519ae34f6c999a2d7404c820da2023-11-24T14:35:17ZengMDPI AGCells2073-44092023-11-011222261410.3390/cells12222614Single-Cell Analysis Differentiates the Effects of p53 Mutation and p53 Loss on Cell Compositions of Oncogenic Kras-Driven Pancreatic CancerXinlei Sun0Daowei Yang1Yang Chen2Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAPancreatic ductal adenocarcinoma (PDAC) is a devastating malignant disease with a dismal prognosis. In the past decades, a plethora of genetically engineered mouse models (GEMMs) with autochthonous pancreatic tumor development have greatly facilitated studies of pancreatic cancer. Commonly used GEMMs of PDAC often harbor the oncogenic KRAS driver mutation (<i>Kras<sup>G12D</sup></i>), in combination with either p53 mutation by knock-in strategy (<i>Trp53<sup>R172H</sup></i>) or p53 loss by conditional knockout (<i>Trp53<sup>cKO</sup></i>) strategy, in pancreatic cell lineages. However, the systematic comparison of the tumor microenvironment between <i>Kras<sup>G12D</sup></i>; <i>Trp53<sup>R172H</sup></i> (KP<sup>mut</sup>) mouse models and <i>Kras<sup>G12D</sup></i>; <i>Trp53<sup>cKO</sup></i> (KP<sup>loss</sup>) mouse models is still lacking. In this study, we conducted cross-dataset single-cell RNA-sequencing (scRNA-seq) analyses to compare the pancreatic tumor microenvironment from KP<sup>mut</sup> mouse models and KP<sup>loss</sup> mouse models, especially focusing on the cell compositions and transcriptomic phenotypes of major cell types including cancer cells, B cells, T cells, granulocytes, myeloid cells, cancer-associated fibroblasts, and endothelial cells. We identified the similarities and differences between KP<sup>mut</sup> and KP<sup>loss</sup> mouse models, revealing the effects of p53 mutation and p53 loss on oncogenic KRAS-driven pancreatic tumor progression.https://www.mdpi.com/2073-4409/12/22/2614pancreatic cancertumor microenvironmentsingle-cell analysis |
| spellingShingle | Xinlei Sun Daowei Yang Yang Chen Single-Cell Analysis Differentiates the Effects of p53 Mutation and p53 Loss on Cell Compositions of Oncogenic Kras-Driven Pancreatic Cancer Cells pancreatic cancer tumor microenvironment single-cell analysis |
| title | Single-Cell Analysis Differentiates the Effects of p53 Mutation and p53 Loss on Cell Compositions of Oncogenic Kras-Driven Pancreatic Cancer |
| title_full | Single-Cell Analysis Differentiates the Effects of p53 Mutation and p53 Loss on Cell Compositions of Oncogenic Kras-Driven Pancreatic Cancer |
| title_fullStr | Single-Cell Analysis Differentiates the Effects of p53 Mutation and p53 Loss on Cell Compositions of Oncogenic Kras-Driven Pancreatic Cancer |
| title_full_unstemmed | Single-Cell Analysis Differentiates the Effects of p53 Mutation and p53 Loss on Cell Compositions of Oncogenic Kras-Driven Pancreatic Cancer |
| title_short | Single-Cell Analysis Differentiates the Effects of p53 Mutation and p53 Loss on Cell Compositions of Oncogenic Kras-Driven Pancreatic Cancer |
| title_sort | single cell analysis differentiates the effects of p53 mutation and p53 loss on cell compositions of oncogenic kras driven pancreatic cancer |
| topic | pancreatic cancer tumor microenvironment single-cell analysis |
| url | https://www.mdpi.com/2073-4409/12/22/2614 |
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