Trellis Single-Cell Screening Reveals Stromal Regulation of Patient-Derived Organoid Drug Responses
DOI10.5281/zenodo.8177571Zenodo8177571MaRDI QIDQ6693701FDOQ6693701
Dataset published at Zenodo repository.
Jahangir Sufi, Jeroen Claus, Petra Vlckova, Maria Zapatero Ramos, Xiao Qin, James W. Opzoomer, Callum Nattress, Daniel Hochhauser, Alexander Tong, Christopher J. Tape, Smita Krishnaswamy, Ferran Cardoso Rodriguez, Rhianna O'Sullivan
Publication date: 24 July 2023
Copyright license: Creative Commons Attribution 4.0 International
Patient-derived organoids (PDOs) can model personalized therapy responses, however current screening technologies cannot reveal drug response mechanisms or how tumor microenvironment cells alter therapeutic performance. To address this, we developed a highly-multiplexed mass cytometry platform to measure post translational modification (PTM) signaling, DNA-damage, cell-cycle activity, and apoptosis in 2,500 colorectal cancer (CRC) PDOs and cancer associated fibroblasts (CAFs) in response to clinical therapies at single-cell resolution. To compare patient- and microenvironment-specific drug responses in thousands of single-cell datasets, we developed Trellis a highly-scalable, hierarchical tree-based treatment effect analysis method. Trellis single-cell screening revealed that on-target cell-cycle blockage and DNA-damage drug effects are common, even in chemorefractory PDOs. However, drug-induced apoptosis is rare, patient-specific, and aligns with cancer cell PTM signaling. We find that CAFs can regulate cancer cell plasticity shifting proliferative stem cells to slow-cycling revival stem cells via YAP to protect cancer cells from chemotherapy. This repo contains the processed scRNA-seq Scanpy AnnData objects generated from the study. More information describing the data can be found at: https://github.com/TAPE-Lab/Ramos-et-al-Trellis
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