Single-cell transcriptomes of pancreatic preinvasive lesions and cancer reveal acinar metaplastic cells’ heterogeneity
| Autor: | Luriano Peters, Osher Amran, Lei Xia, Dror Kolodkin-Gal, Roy Zvi Granit, Abdelmajeed Nasereddin, Oshri Yosefov-Levi, Idit Shiff, Gideon Zamir, Karine Atlan, Yehuda Schlesinger, Rachel Kalifa, Yuval Nevo, Oren Parnas, Sharona Elgavish |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Biopsy Cellular differentiation Cell General Physics and Astronomy Acinar Cells Kaplan-Meier Estimate Animals Genetically Modified Mice 0302 clinical medicine Single-cell analysis Metaplasia Tumor Microenvironment Cancer genomics RNA-Seq lcsh:Science Cancer Multidisciplinary Cell Differentiation Forkhead Transcription Factors Gene Expression Regulation Neoplastic medicine.anatomical_structure 030220 oncology & carcinogenesis Female Single-Cell Analysis medicine.symptom Carcinoma Pancreatic Ductal Cell type Stromal cell Science Tumour heterogeneity Immunology Biology Article General Biochemistry Genetics and Molecular Biology Proto-Oncogene Proteins p21(ras) Genetic Heterogeneity 03 medical and health sciences Pancreatectomy Pancreatic cancer medicine Acinar cell Animals Humans Pancreas Homeodomain Proteins General Chemistry medicine.disease Pancreatic Neoplasms Disease Models Animal 030104 developmental biology Mutation Cancer research lcsh:Q Precancerous Conditions Transcription Factors |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-18 (2020) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-18207-z |
| Popis: | Acinar metaplasia is an initial step in a series of events that can lead to pancreatic cancer. Here we perform single-cell RNA-sequencing of mouse pancreas during the progression from preinvasive stages to tumor formation. Using a reporter gene, we identify metaplastic cells that originated from acinar cells and express two transcription factors, Onecut2 and Foxq1. Further analyses of metaplastic acinar cell heterogeneity define six acinar metaplastic cell types and states, including stomach-specific cell types. Localization of metaplastic cell types and mixture of different metaplastic cell types in the same pre-malignant lesion is shown. Finally, single-cell transcriptome analyses of tumor-associated stromal, immune, endothelial and fibroblast cells identify signals that may support tumor development, as well as the recruitment and education of immune cells. Our findings are consistent with the early, premalignant formation of an immunosuppressive environment mediated by interactions between acinar metaplastic cells and other cells in the microenvironment. Pancreatic ductal adenocarcinoma may be initiated by acinar metaplasia, but the molecular and cellular insights during this transition are unclear. Here the authors show, using single cell RNA-sequencing analyses, that mouse metaplastic acinar cells can be clustered into six cell types or states that are heterogeneous and have unique transcription programs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|