Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses.

ABSTRACT: Cellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances in single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles to the cellular activities underlying cancer. Here, we present an integrated experimental system that connects single cell gene expression to heterogeneous cancer cell growth, metastasis, and treatment response. Our system integrates single cell transcriptome profiling with DNA barcode based clonal tracking in patient-derived xenograft models. We show that leukemia cells exhibiting unique gene expression respond to different chemotherapies in distinct but consistent manners across multiple mice. In addition, we uncover a form of leukemia expansion that is spatially confined to the

SUBMITTER: Contreras-Trujillo H 

PROVIDER: S-EPMC8586369 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature