Single nuclear RNA sequencing and 10X spatial transcriptomic profiling of murine tumors initiated by transplantation of engineered prostate organoids [snRNA-seq]

Single-nuclear RNA-sequencing of murine organoid transplant-derived prostate tumors. Purpose: To identify differences in cell composition in murine prostatic tumors and to generate a reference dataset of all major cell types present in mouse prostate tumors Results: We recovered 4,872 cells with a median of 7055.5 UMIs per cell. Conclusions: snRNASeq reveals heterogeneity within neuroendocrine prostate cancer compartment, dominated by an Ascl1+ expression profile with mixed luminal lineage marker genes. snRNASeq recovers all the major epithelial, immune, and stromal cell types in prostate tumors. Spatial transcriptomic profiling of murine prostate tumors. Purpose: To spatially map the major cell types in the mouse prostatic tumors and identify spatially distinct neuroendocrine tumor compartments. Distinct tumor microenvironments were also used for identification of cell:cell signaling axes distributed between the histological subtypes. Conclusions: Spatial transcriptomic profiling of the mouse prostate reveals all major cell types and allows for cell:cell signaling analyses upon integration with our matching snRNA-Seq data Overall design: One RPM tumor was isolated from a mouse at 10 weeks post transplantation, when the neuroendocrine transition was expected to be fully penetrant. This tumor (RR1818) was flash frozen and processed for single nuclear RNA sequencing to capture all cell types within tumors and generate a reference dataset. For Visium: 4 biologically independent RPM tumors (primary mouse prostate tumor and metastatic lymph node) at different stages of the adeno-to-neuroendocrine transdifferentiation process were used for this analysis. RPM tumors isolated from 2 weeks (RR1104), 3 weeks (RR1105 and RR1107), 4weeks (RR1109), 6 weeks (RR1117 and RR1118), and 10 weeks (RR1123, RR1132, RR1124, and RR1128) were isolated and processed for 10X Visium in technical replicates. No treatments applicable.