Faculty, Staff and Student Publications
Publication Date
8-1-2024
Journal
Clinical Cancer Research
Abstract
Purpose: The genetic intratumoral heterogeneity observed in human osteosarcomas poses challenges for drug development and the study of cell fate, plasticity, and differentiation, which are processes linked to tumor grade, cell metastasis, and survival.
Experimental design: To pinpoint errors in osteosarcoma differentiation, we transcriptionally profiled 31,527 cells from a tissue-engineered model that directs mesenchymal stem cells toward adipogenic and osteoblastic fates. Incorporating preexisting chondrocyte data, we applied trajectory analysis and non-negative matrix factorization to generate the first human mesenchymal differentiation atlas.
Results: This "roadmap" served as a reference to delineate the cellular composition of morphologically complex osteosarcoma tumors and quantify each cell's lineage commitment. Projecting a bulk RNA-sequencing osteosarcoma dataset onto this roadmap unveiled a correlation between a stem-like transcriptomic phenotype and poorer survival outcomes.
Conclusions: Our study quantifies osteosarcoma differentiation and lineage, a prerequisite to better understanding lineage-specific differentiation bottlenecks that might someday be targeted therapeutically.
Keywords
Osteosarcoma, Humans, Cell Differentiation, Mesenchymal Stem Cells, Bone Neoplasms, Single-Cell Analysis, Transcriptome, Cell Lineage, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Gene Expression Profiling
DOI
10.1158/1078-0432.CCR-24-0563
PMID
38775859
PMCID
PMC11293971
PubMedCentral® Posted Date
2-1-2025
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
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Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons