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Epithelial plasticity can generate multi-lineage phenotypes in human and murine bladder cancers
- Source :
- Nature Communications, Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020)
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group UK, 2020.
-
Abstract
- Tumor heterogeneity is common in cancer, however recent studies have applied single gene expression signatures to classify bladder cancers into distinct subtypes. Such stratification assumes that a predominant transcriptomic signature is sufficient to predict progression kinetics, patient survival and treatment response. We hypothesize that such static classification ignores intra-tumoral heterogeneity and the potential for cellular plasticity occurring during disease development. We have conducted single cell transcriptome analyses of mouse and human model systems of bladder cancer and show that tumor cells with multiple lineage subtypes not only cluster closely together at the transcriptional level but can maintain concomitant gene expression of at least one mRNA subtype. Functional studies reveal that tumor initiation and cellular plasticity can initiate from multiple lineage subtypes. Collectively, these data suggest that lineage plasticity may contribute to innate tumor heterogeneity, which in turn carry clinical implications regarding the classification and treatment of bladder cancer.<br />Recent studies have utilized bulk tumour mRNA sequencing to classify bladder cancers into distinct subgroups. Here, the authors use single cell transcriptomic analysis and cell transplant studies to show that epithelial plasticity can generate basal, luminal and mesenchymal phenotypes in human and murine bladder cancers.
- Subjects :
- 0301 basic medicine
Lineage (genetic)
Science
Cell Plasticity
General Physics and Astronomy
Tumor initiation
Urological cancer
Biology
Integrin alpha6
General Biochemistry, Genetics and Molecular Biology
Article
Transcriptome
03 medical and health sciences
Mice
0302 clinical medicine
Single-cell analysis
medicine
Biomarkers, Tumor
Animals
Humans
Cell Lineage
lcsh:Science
Cancer
Regulation of gene expression
Multidisciplinary
Bladder cancer
Gene Expression Profiling
General Chemistry
medicine.disease
Gene expression profiling
Gene Expression Regulation, Neoplastic
030104 developmental biology
Cell Transformation, Neoplastic
Phenotype
Urinary Bladder Neoplasms
030220 oncology & carcinogenesis
Cancer research
Keratin-5
lcsh:Q
Single-Cell Analysis
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....2cfd5f33988e3d521157bc3c2b69987c