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

Nat Commun
Publication Year: 
Humberto Contreras-Trujillo
Jiya Eerdeng
Samir Akre
Du Jiang
Jorge Contreras
Basia Gala
Mary C Vergel-Rodriguez
Yeachan Lee
Aparna Jorapur
Areen Andreasian
Lisa Harton
Charles S Bramlett
Anna Nogalska
Gang Xiao
Jae-Woong Lee
Lai N Chan
Markus Muschen
Akil A Merchant
Rong Lu
PubMed link: 
Public Summary: 
This publication uses single-cell tracking to describe how expansion of blood stem cells can lead to leukemia.
Scientific 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 bone marrow of single anatomical sites and driven by cells with distinct gene expression. Our integrated experimental system can interrogate the molecular and cellular basis of the intratumoral heterogeneity underlying disease progression and treatment resistance.