Abstract:
Cancers share common cellular and physiological features. Little is known about whether distinctive gene expression patterns can be displayed at the single-cell level by gene families in cancer cells. The expression of gene homologs within a family can exhibit concurrence and exclusivity. Concurrence can promote all-or-none expression patterns of related genes and underlie alternative physiological states. Conversely, exclusive gene families express the same or similar number of homologs in each cell, allowing a broad repertoire of cell identities to be generated. We show that gene families involved in the cell-cycle and antigen presentation are expressed concurrently. Concurrence in the DNA replication complex MCM reflects the replicative status of cells, including cell lines and cancer-derived organoids. Exclusive expression requires precise regulatory mechanism, but cancer cells retain this form of control for ion homeostasis and extend it to gene families involved in cell migration. Thus, the cell adhesion-based identity of healthy cells is transformed to an identity based on migration in the population of cancer cells, reminiscent of epithelial-mesenchymal transition.
摘要:
癌症具有共同的细胞和生理特征。对于癌细胞中的基因家族是否可以在单细胞水平上展示独特的基因表达模式知之甚少。家族内基因同源物的表达可以表现出并发性和排他性。并发可以促进相关基因的全或无表达模式,并成为替代生理状态的基础。相反,专有基因家族在每个细胞中表达相同或相似数量的同源物,允许产生广泛的细胞身份。我们表明,参与细胞周期和抗原呈递的基因家族同时表达。在DNA复制复合体MCM中的并发反映了细胞的复制状态,包括细胞系和源自癌症的类器官。独占表达需要精确的调控机制,但是癌细胞保留了这种形式的离子稳态控制,并将其扩展到参与细胞迁移的基因家族。因此,健康细胞的基于细胞粘附的身份转化为基于癌细胞群体迁移的身份,让人想起上皮-间质转化。