Poster abstracts
Poster number 16 submitted by Yogesh Budhathoki
Unraveling Osteosarcoma Complexity: Constructing a Specialized Single-Cell Atlas for Accurate and Reliable Cell Type Annotation
Yogesh Budhathoki (Molecular, Cellular, and Developmental Biology, The Ohio State University), Matthew Cannon (Nationwide Childrens Hospital), Amy Gross (Nationwide Childrens Hospital), Anand Patel (St. Jude Childrens Research Hospital), Troy A. McEachron (National Institutes of Health), Meran Cam (Nationwide Childrens Hospital)
Abstract:
Osteosarcoma is an aggressive bone malignancy that poses considerable treatment challenges primarily due to high intra-tumoral heterogeneity, structural genomic complexity, and tendency to metastasize to the lungs. Patients with aggressive osteosarcoma tend to show temporary positive reactions to chemotherapy, only to suffer relapses shortly after the treatment, frequently accompanied by lung metastases. To grasp the reasons behind this resistance and relapse, it is crucial to understand the heterogeneity among tumor cells and their surroundings.
Single-cell RNA sequencing has allowed the scientific community to classify and characterize each osteosarcoma cell at the transcriptome level. However, a lack of a reliable and standardized cell type annotation reference for the heterogenous intra-tumor cell populations and surrounding microenvironments poses a significant challenge for efficient research.
We have begun a collaborative effort to systematically evaluate the inter- and intra-tumor heterogeneity inherent to osteosarcoma cells and to build a comprehensive reference atlas. This reference would facilitate the characterization of distinct cell populations within the tumor and the tumor-interacting “normal” cells, which often adopt phenotypes markedly different from their non-tumor-associated counterparts. We have assembled over 500,000 cells from patients, patient-derived xenografts, and key mouse models to make our reference universally applicable. We have agreed with several other laboratories to grow the reference dataset depth.
Our preliminary results have identified consistent patterns of intra-tumoral heterogeneity that are recurrent and predictable. Some tumor cell types have immature proliferative stem cell-like features, while others have inflammatory or matrix-forming osteoblast- and fibroblast-like phenotypes. Accurate and thoughtful references, endorsed by a collaborative group of scientific leaders in osteosarcoma research, will accelerate discovery by creating a standard reference and harmonized language for discussing the osteosarcoma-specific tumor microenvironment, the surrounding environment, and the treatment effects.
References:
Additional Authors:
Melissa Sammons (Nationwide Children's Hospital)
Lindsay Ryan (Nationwide Children's Hospital)
Keywords: matastasis, tumoral heterogeneity, xenografts