Figure 4.

Stem cell proliferation, self-renewal, differentiation, and transformation. Depicted here is a hypothetical long-term stem cell (LT-SC), which has the greatest self-renewal activity and is quiescent in its niche (bottom). LT-SC develops into a short-term stem cell (ST-SC), which shows reduced self-renewal activity but increased proliferation. The ST-SC then gives rise to early progenitor cells that may have lost self-renewal capacity, but probably represent the most proliferative cell population. Early progenitors generate late progenitor cells that begin to commit to differentiate by expressing lineage-specific differentiation markers and these late progenitor cells gradually develop into fully differentiated cells that once again lose proliferative potential (i.e., post-mitotic). From the standpoint of transformation probability, the ST-SC that retains self-renewal activity and progenitor cells that are highly proliferative (demarcated by two vertical thick lines) theoretically could represent the best targets for tumorigenic transformation.