Fitness and transcriptional plasticity of human breast cancer single-cell-derived clones.
Loading...
Embargo End Date
ICR Authors
Authors
Nguyen, LV
Eyal-Lubling, Y
Guerrero-Romero, D
Kronheim, S
Chin, S-F
Manzano Garcia, R
Sammut, S-J
Lerda, G
Lui, AJW
Bardwell, HA
Greenwood, W
Shin, HJ
Masina, R
Kania, K
Bruna, A
Esmaeilishirazifard, E
Kolyvas, EA
Aparicio, S
Rueda, OM
Caldas, C
Eyal-Lubling, Y
Guerrero-Romero, D
Kronheim, S
Chin, S-F
Manzano Garcia, R
Sammut, S-J
Lerda, G
Lui, AJW
Bardwell, HA
Greenwood, W
Shin, HJ
Masina, R
Kania, K
Bruna, A
Esmaeilishirazifard, E
Kolyvas, EA
Aparicio, S
Rueda, OM
Caldas, C
Document Type
Journal Article
Date
2025-05-27
Date Accepted
2025-04-23
Abstract
Clonal fitness and plasticity drive cancer heterogeneity. We used expressed lentiviral-based cellular barcodes combined with single-cell RNA sequencing to associate single-cell profiles with in vivo clonal growth. This generated a significant resource of growth measurements from over 20,000 single-cell-derived clones in 110 xenografts from 26 patient-derived breast cancer xenograft models. 167,375 single-cell RNA profiles were obtained from 5 models and revealed that rare propagating clones display a highly conserved model-specific differentiation program with reproducible regeneration of the entire transcriptomic landscape of the original xenograft. In 2 models of basal breast cancer, propagating clones demonstrated remarkable transcriptional plasticity at single-cell resolution. Dichotomous cell populations with different clonal growth properties, signaling pathways, and metabolic programs were characterized. By directly linking clonal growth with single-cell transcriptomes, these findings provide a profound understanding of clonal fitness and plasticity with implications for cancer biology and therapy.
Citation
Cell reports, 2025, 44 (5), pp. 115699 -
Source Title
Cell reports
Publisher
CELL PRESS
ISSN
2211-1247
eISSN
2211-1247
Collections
Research Team
Cancer Dynamics