生物
转录组
谱系(遗传)
膀胱癌
谱系标记
表型
癌症研究
基因表达谱
癌症
基因表达
计算生物学
基因
遗传学
作者
John P. Sfakianos,Jorge Daza,Yang Hu,Harry Anastos,Geoffrey Bryant,Rohan Bareja,Ketan K. Badani,Matthew D. Galsky,Olivier Elemento,Bishoy Faltas,David J. Mulholland
标识
DOI:10.1038/s41467-020-16162-3
摘要
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.
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