Nanog-induced dedifferentiation of p53-deficient mouse astrocytes into brain cancer stem-like cells

Self-renewal, differentiation, and tumorigenicity characterize cancer stem cells (CSCs), which are rare and maintained by specific cell fate regulators. CSCs are isolated from glioblastoma multiforme (GBM) and may be responsible for the lethality of incurable brain tumors. Brain CSCs may arise from the transformation of undifferentiated, nestin-positive neural stem or progenitor cells and GFAP-expressing astrocytes. Here, we report a role of Nanog in the genesis of cancer stem-like cells. Using primary murine p53-knockout astrocytes (p53−/− astrocytes), we provide evidence that enforced Nanog expression can increase the cellular growth rate and transform phenotypes in vitro and in vivo. In addition, Nanog drives p53−/− astrocytes toward a dedifferentiated, CSC-like phenotype with characteristic neural stem cell/progenitor marker expression, neurosphere formation, self-renewal activity, and tumor development. These findings suggest that Nanog promotes dedifferentiation of p53-deficient mouse astrocytes into cancer stem-like cells by changing the cell fate and transforming cell properties.

► We investigate a role of Nanog in the genesis of cancer stem-like cells.
► Nanog is expressed in human GBM cell lines and can drive transformation of murine p53−/− astrocytes.
► Nanog drives the dedifferentiation of p53−/− astrocytes into cancer stem-like cells.
► These results suggest that Nanog promotes dedifferentiation of p53-deficient mouse astrocytes into cancer stem-like cells by.