A comprehensive transcriptome portrait of colorectal cancer derived organoid at single cell levels (Single cell RNA-seq)

Due to the highly heterogeneous nature of tumor, it is very challenging to study the molecular mechanisms of tumorigenesis. Recently, in vitro derived 3D organoid culture system were developed and may serve as a good model for studing the cancer molecular mechanisms in vitro, which allows long-term expansion of human colorectal colon cancer. To fully evaluate the organoid culture system, we perform a single cell RNA-seq survey of 4,792 single cells of tumor and adjacent normal tissues in vivo as well as corresponding patient-derived organoid samples from seven patients with colon cancer to investigate their gene expression signatures. We also apply whole-exon sequencing, whole genome sequencing and Sanger sequencing to characterize their genomic features accordingly. We found that tumor-derived organoid in vitro in general faithfully maintained the gene expression signatures, gene regulatory network, tumor-microenvironment cross-talk, as well as mutations such as copy number variants and point mutations of tumor cells in vivo. However adjacent normal tissue-derived organoid, despite remaining normal in genomic levels, changed their gene expression profiles drastically and acquired tumor-like gene expression signatures. Overall design: Single cell transcriptome profiles of tumor and adjacent normal tissues in vivo as well as corresponding patient-derived organoid samples from seven patients with colon cancer were generated by next generation sequencing using illumina 4000.