Stem cell hierarchies

Hierarchies of division-competent cells have been demonstrated in other adult tissues, such as blood and the small intestine (44,45). These hierarchies comprise a primary tissue-specific stem cell that can produce all the cell types of the tissue, including new stem cells. Downstream of the primary stem cell are more restricted progenitors that give rise only to a subset of cell types, and then there are lineage-committed progenitors that produce only one particular cell type. The number of committed progenitors and the number of divisions between them and the primary stem cells varies accord ing to the tissue. For example, there are a large number of increasingly committed progenitors in the hematopoietic system because a correspondingly large number of differentiated cell types need to be produced (44). In contrast, there appears to be only one type of progenitor downstream of the primary keratinocyte stem cell in the skin (45).

It is still not clear how many and what type of committed progenitors may be present in the mammary epithelium. However, the results of the studies presented above suggest that there are at least two layers of commitment downstream of the primary stem cell: The first is the commitment to produce either ducts or lobules, and the second is commitment to produce either luminal or myoepithelial cells (see Fig. 1).

The data derived from studies on DNA label retention, Hoechst 33342 efflux, and Sca-1 expression in the mouse mammary gland labeled during pubertal development support the suggestion that the stem cell population is heterogeneous (39). The population positive for Sca-1 contains at least two different cell types, SP-positive LRCs and those that are neither LRCs nor SP cells. Welm and colleagues suggested that the Sca-1-positive population, LRCs, and SP cells represent the most primitive population that may contain the multipotent stem cells (39). The steroid receptor-positive LRCs identified by Zeps and in our study in adult mouse and human mammary epithelium could be more committed or lineage-restricted stem cells (38,40).

0 0

Post a comment