Figure 2.

RB function in adult stem cells. Simplified view of an RB wild-type adult organ, with quiescent populations of stem cells (SCs) giving rise to proliferating progenitor cells (PCs) that can exit the cell cycle to generate differentiated cells (DC) and terminally differentiated cells (TDCs). In an RB mutant (or RB family mutant) context, exit from quiescence and increased numbers are often observed in stem cell populations, and increased proliferation is often present in progenitor cells. In some cases, this increased proliferation is accompanied by increased cell death, especially as progenitors are induced to enter a differentiation program. Loss of RB also leads to a reduced capacity to differentiate and terminally differentiate in some lineages. Finally, RB inactivation may favor certain cellular fates by default (no death and no decrease in differentiation potential) or actively (by activation of a program of genes); however, loss of RB often prevents terminal differentiation. Eventually, although stem cells and progenitor cells may be the cell populations that are initially responsive to loss of RB in adult tissues and organs, tumors initiated by loss of RB may be mostly composed of cells with differentiated characteristics (“differentiated cancer”).