Colorectal cancer stem cell states uncovered by simultaneous single-cell analysis of transcriptome and telomeres

Here, simultaneous measurement of telomere length and transcriptome in the same cells enable systematic assessment of CSCs in primary colorectal cancer (CRC). The in-depth transcriptome profiled by SMART-seq2 is independently validated by high-throughput scRNA-seq using 10x Genomics. We find that rare CSCs exist in dormant state and display plasticity towards cancer epithelial cells (EPCs) that essentially are presumptive tumor-initiating cells (TICs), while both retaining the prominent signaling pathways including WNT, TGF-b and HIPPO/YAP. Moreover, CSCs exhibit chromosome copy number variation (CNV) pattern resembling cancer EPCs but distinct from normal stem cells, suggesting the phylogenetic relationship between CSCs and cancer EPCs. Notably, CSCs maintain shorter telomeres and possess minimal telomerase activity consistent with their non-proliferative nature, unlike cancer EPCs.