Fig. 1. Classical stem cell hierarchy. Model of the `classical' hierarchy of undifferentiated epithelial stem cell, transit amplifying (TA) progenitor cells and mature postmitotic differentiated cells. Cell fate choices are indicated by red arrows. In this model, the stem cell in its `niche' and different TA cell subclasses can self-renew (curved arrows). Stem cells self-renew infrequently and TA cells more rapidly. Early TA cells may be able to replace stem cells if the niche is depleted (dashed arrow 1). The niche probably consists of several cell types and associated molecules, including blood vessels and nerves. `Transdifferentiation' of one well-defined differentiated cell type into another could occur directly, without cell division (dashed arrow 2) or might also involve reversion or de-differentiation between distinct TA progenitor populations (dashed arrows 3). Rarely, stem cells switch from one tissue-specific lineage to another (dashed arrow 4) in a process called metaplasia or transdetermination (see Box 1). Adapted, with permission, from Watt and Hogan (Watt and Hogan, 2000).