The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity
Cancer arises from clonal expansion of a single cell. Yet, most human cancers are characterized by extensive intratumor heterogeneity and comprise various subpopulations of cells with distinct phenotypes and biological properties. Intratumor heterogeneity poses major challenges in understanding cancers, managing patients, and designing effective treatment strategies. Functional heterogeneity within individual tumors is partly due to the presence of genetically distinct subclonal cell populations. Furthermore, interactions between cancer cells and the tumor microenvironment can alter the phenotype of cancer cells via nongenetic mechanisms. The combination of cell-intrinsic and cell-extrinsic changes occurring during tumor growth generates functionally distinct subsets of cells that differentially contribute to tumor maintenance.