| HRA001252
(Controlled Access)
|
We adopted single-cell RNA-Seq method to analyze 8,085 cells from matching adjacent normal tissues, primary tumors, and metastatic tumors of 11 metastatic colorectal cancer patients. Furthermore, for two of the patients, we combined single-cell RNA sequencing and single-cell point mutation identification by cDNA Sanger sequencing, which permit us to identify the important phenotypic differences between the cancer cells with and without critical point mutations in the same patient in vivo at single-cell resolution. The PPAR signaling pathway was activated in tumors, and inhibiting it could drastically inhibit the growth of CRC organoids in vitro. Notably, distinct origins of lymph nodes and liver metastases were revealed in the same patients, which were verified by both CNVs and mitochondrial mutation profiles at single-cell resolution. Our study elucidates molecular heterogeneity of CRC as well as potential therapeutic target for CRC therapy. |
