10 × Genomics Flex Gene Expression is a powerful tool for single-cell transcriptomics of xenografts models

The 10 × Genomics Flex Gene Expression protocol is a probe-based method that profiles fixed or frozen material, simplifying sample handling before scRNA-seq. Although probes exist only for human and mouse, we show that xenograft samples containing mixed human-mouse cells can be profiled by combining both probe sets in a single reaction. Cellranger generates species-specific count tables in which specific probes strongly outperform cross-reactive ones. We implement an approach to remove cross-reactive signals, yielding clean species-specific matrices. This solution enables scRNA-seq of xenografts without flow sorting and supports analysis of both the graft and its microenvironment.