Figure 2.

Intra-tumoral heterogeneity (ITH) of EPN in the cancer stem cell (CSC) perspective. (a) Schematics of the classical (on the left) and plasticity (on the right) CSC model. The classical CSC model asserts that CSCs are a rare fraction of the bulk tumor, able to self-renew and to differentiate along multiple lineages, driving unidirectional hierarchy of heterogeneous cells. CSC plasticity model proposes that cancer cells can dynamically transition from a CSC state to a non-CSC state and vice versa. Combinatorial dynamics of genetic and epigenetic alterations and distinct microenvironmental contexts engender cell stemness and plasticity, installing ITH. (b) CSC model(s) in intra-cranial ependymomagenesis. Molecular events occurring in distinct cells of origin drive ependymomagenesis in the two compartments: genomic instability, leading to chromothripsis, gene fusions, and INK4a-ARF deletions, predominate in ST-RELA, whereas epigenetic factors (e.g., CIMP phenotype, global loss of H3K27me3, EZHIP overexpression) predominate in PFA.