In-situ multiomics analysis reveals only minor genetic and epigenetic changes in human liver cancer stem cells

Abstract Cancer stem cells (CSCs) play pivotal roles in human cancer but their genetic and epigenetic changes are still largely unknown. Here we show that human CSCs are more similar to paratumor cells in liver cancer. Using single-cell-based in-situ multiomics analysis, we found that although liver CSCs (LCSCs) from patients had some potential key genetic and epigenetic changes in their genome, they had substantially fewer somatic single nucleotide variants (SNVs), copy number alterations (CNAs) and differentially methylated regions, and less change in the global levels of DNA cytosine modifications, than other tumor parenchymal cells. The cluster analysis of SNVs, CNAs and DNA methylation patterns and spatial transcriptomes all clearly showed that the LCSCs were clustered with the paratumor liver cells. Thus, only minor genetic and epigenetic changes occurred in human LCSCs. Targeting key changes in CSCs, not just changes in bulk tumor cells, should be more effective for human cancer therapy.