Single-cell analysis of XXXX cell lines reveals diverse expression patterns of individual cells invoked by a molecular target drug treatment.

@entity8958 @entity5 @entity470 @entity4733 @entity4149 @entity2220
BACKGROUND: To understand the heterogeneous behaviors of individual @entity5 cells, it is essential to investigate gene expression levels as well as their divergence between different individual cells. Recent advances in next-generation sequencing-related technologies have enabled us to conduct a single-cell RNA-Seq analysis of a series of @entity2220 cell lines. RESULTS: We analyze a total of 336 single-cell RNA-Seq libraries from seven cell lines. The results are highly robust regarding both average expression levels and the relative gene expression differences between individual cells. Gene expression diversity is characteristic depending on genes and pathways. Analyses of individual cells treated with the multi- @entity4149 kinase inhibitor @entity4733 reveal that, while the ribosomal genes and many other so-called house-keeping genes reduce their relative expression diversity during the drug treatment, the genes that are directly targeted by @entity4733 , the @entity470 and @entity8958 genes, remain constant. Rigid transcriptional control of these genes may not allow plastic changes of their expression with the drug treatment or during the cellular acquisition of drug resistance. Additionally, we find that the gene expression patterns of @entity5 -related genes are sometimes more diverse than expected based on the founder cells. Furthermore, we find that this diversity is occasionally latent in a normal state and initially becomes apparent after the drug treatment. CONCLUSIONS: Characteristic patterns in gene expression divergence, which would not be revealed by transcriptome analysis of bulk cells, may also play important roles when cells acquire drug resistance, perhaps by providing a cellular reservoir for gene expression programs.
