Heterogeneity in the cancer stem cell population in glioblastoma

Glioblastoma (GBM) is the most aggressive form of glioma. Over the past decade, several lines of evidence have indicated that not every cell in these tumors is equal. Another way to state this is that some tumor cells in GBM are more important than the rest. In biological terms, this inequality translates into a cellular hierarchy, whose apex is occupied by cancer stem cells.

Throughout the body, tissue homeostasis is maintained by stem cells that generate defined lineages of specialized differentiated cells. Not surprisingly, GBM tumors are remarkably complex at the histologic level, which begs the question: Does a single cell type with stem-like properties produce the entire spectrum of tumor lineages and histologies or is the cancer stem cell population heterogeneous?

Using human GBM cultures, we recently discovered that within any given GBM tumor there are multiple tumor cell types that fulfill stem cell criteria. These cell types manifest striking transcriptional and metabolic differences, in addition to discreet differentiation programs that allow them to not only adapt to diverse microenvironmental conditions, but also shape the niches where they reside.