Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses.
Nat Commun
; 12(1): 6522, 2021 11 11.
Article
in En
| MEDLINE
| ID: mdl-34764253
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Single-Cell Analysis
/
Transcriptome
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2021
Document type:
Article
Affiliation country: