Mapping the Single-cell Differentiation Landscape of Osteosarcoma.
Clin Cancer Res
; 2024 May 22.
Article
en En
| MEDLINE
| ID: mdl-38775859
ABSTRACT
PURPOSE:
The genetic intratumoral heterogeneity observed in human osteosarcomas (OS) poses challenges for drug development and the study of cell fate, plasticity, and differentiation, processes linked to tumor grade, cell metastasis, and survival. EXPERIMENTALDESIGN:
To pinpoint errors in OS differentiation, we transcriptionally profiled 31,527 cells from a tissue-engineered model that directsMSCs toward adipogenic and osteoblastic fates. Incorporating pre-existing chondrocyte data, we applied trajectory analysis and non-negative matrix factorization (NMF) to generate the first human mesenchymal differentiation atlas.RESULTS:
This 'roadmap' served as a reference to delineate the cellular composition of morphologically complex OS tumors and quantify each cell's lineage commitment. Projecting a bulk RNA-seq OS dataset onto this roadmap unveiled a correlation between a stem-like transcriptomic phenotype and poorer survival outcomes.CONCLUSIONS:
Our study quantifies OS differentiation and lineage, a prerequisite to better understanding lineage-specific differentiation bottlenecks that might someday be targeted therapeutically.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos