Deconvolution of Cell Type-Specific Drug Responses in Human Tumor Tissue with Single-Cell RNA-seq
Deconvolution of Cell Type-Specific Drug Responses in Human Tumor Tissue with Single-Cell RNA-seq
Precision oncology requires the timely selection of effective drugs for individual patients. An ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity. Here we combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses. We applied this approach to glioblastoma (GBM) and demonstrated that acute slice cultures from individual patients recapitulate the cellular and molecular features of the originating tumor tissue. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients, including unexpected effects on the immune microenvironment. We anticipate that this approach will facilitate rapid, personalized drug screening to identify effective therapies for solid tumors.
Zhao Wenting、Dovas Athanassios、Otten Marc L.、Sisti Michael、Bruce Jeffrey N.、Canoll Peter、Spinazzi Eleonora Francesca、Marie Tamara、Sudhakar Tejaswi、Levitin Hanna Mendes、Upadhyayula Pavan、Sims Peter A.
Department of Systems Biology, Columbia University Irving Medical CenterDepartment of Pathology & Cell Biology, Columbia University Irving Medical CenterDepartment of Neurological Surgery, Columbia University Irving Medical CenterDepartment of Neurological Surgery, Columbia University Irving Medical CenterDepartment of Neurological Surgery, Columbia University Irving Medical CenterDepartment of Pathology & Cell Biology, Columbia University Irving Medical CenterDepartment of Neurological Surgery, Columbia University Irving Medical CenterDepartment of Pathology & Cell Biology, Columbia University Irving Medical CenterDepartment of Neurological Surgery, Columbia University Irving Medical CenterDepartment of Systems Biology, Columbia University Irving Medical CenterDepartment of Neurological Surgery, Columbia University Irving Medical CenterDepartment of Systems Biology, Columbia University Irving Medical Center||Sulzberger Columbia Genome Center, Columbia University Irving Medical Center||Department of Biochemistry & Molecular Biophysics, Columbia University Irving Medical Center
医学研究方法肿瘤学细胞生物学
Zhao Wenting,Dovas Athanassios,Otten Marc L.,Sisti Michael,Bruce Jeffrey N.,Canoll Peter,Spinazzi Eleonora Francesca,Marie Tamara,Sudhakar Tejaswi,Levitin Hanna Mendes,Upadhyayula Pavan,Sims Peter A..Deconvolution of Cell Type-Specific Drug Responses in Human Tumor Tissue with Single-Cell RNA-seq[EB/OL].(2025-03-28)[2025-05-01].https://www.biorxiv.org/content/10.1101/2020.04.22.056341.点此复制
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