Mapping the single-cell differentiation landscape of osteosarcoma Journal Article
| Authors: | Truong, D. D.; Weistuch, C.; Murgas, K. A.; Admane, P.; King, B. L.; Lee, J. C.; Lamhamedi-Cherradi, S. E.; Swaminathan, J.; Daw, N. C.; Gordon, N.; Gopalakrishnan, V.; Gorlick, R. G.; Somaiah, N.; Deasy, J. O.; Mikos, A. G.; Tannenbaum, A.; Ludwig, J. |
| Article Title: | Mapping the single-cell differentiation landscape of osteosarcoma |
| 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. © 2024 American Association for Cancer Research. |
| Keywords: | osteosarcoma; cancer survival; controlled study; bone neoplasms; survival analysis; bone tumor; human cell; genetics; mortality; microscopy; nonhuman; cancer grading; genetic analysis; mouse; metabolism; metastasis; gene expression; gene expression profiling; animal experiment; cell fate; cell differentiation; pathology; cell line, tumor; transcriptomics; cell lineage; gene expression regulation; gene expression regulation, neoplastic; algorithm; tumor cell line; mesenchymal stem cell; transcriptome; rna sequence; mesenchymal stem cells; plasticity; single cell analysis; single-cell analysis; procedures; humans; human; male; article; rna sequencing; differential gene expression; single cell differentiation |
| Journal Title: | Clinical Cancer Research |
| Volume: | 30 |
| Issue: | 15 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2024-08-01 |
| Start Page: | 3259 |
| End Page: | 3272 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-24-0563 |
| PUBMED: | 38775859 |
| PROVIDER: | scopus |
| PMCID: | PMC11293971 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work