AI Article Synopsis
- * Researchers profiled over 31,000 cells to create a differentiation map of mesenchymal stem cells, revealing insights into how they develop into various cell types.
- * The findings suggest a link between certain stem-like cell characteristics and poor survival, highlighting the potential for targeted therapies aimed at overcoming differentiation issues in osteosarcoma.
Article 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293971 | PMC |
| http://dx.doi.org/10.1158/1078-0432.CCR-24-0563 | DOI Listing |
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