Features of cancer stem cells in colorectal tumors revealed by complex single cell analysis

Tumor recurrence and metastasis remain unavoidable due to a distinct tumor subpopulation known as cancer stem cells (CSCs). To explore the unique cell types contribute to colorectal cancer (CRC) progression, we profiled 831 single cells by simultaneous analysis of RNA sequencing (scRNA-seq) and telomere length in the same cell. Specific markers CD44, CD133 and LGR5 were used to enrich. We find small subpopulations with special features including quiescent CSCs, and epithelial lineage cancer cells (EPCs). Those quiescent CSCs have distinct features including higher level of pluripotency and Wnt signature, and shorter telomeres. Lineage tracing analysis showed that quiescent CSCs could plasticized and generate to epithelial lineage cancer cells with high proliferation and telomeres elongation, and these cells could also transform to each other. New marker genes for CSCs were identified including PROX1, TNFRSF19 and SMOC2. Survival analysis revealed that higher signatures of CSCs and EPCs predicts poor clinical outcome in CRC patients and could be a prognostic biomarkers. These findings provide insight into molecular classification of colorectal cancers and telomere function in CSCs.

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