Tissue stem cells: new tools and functional diversity

Abstract

The detailed understanding of adult tissue stem cells has significance for both regenerative medicine and oncology. This perspective will discuss how major advances in our ability to identify and monitor these cells, which include genetic lineage tracing, FACS purification, and robust in vitro clonogenic assays, have changed our view of their roles in many organs. Label retention and quiescence are no longer considered obligatory stem cell features. Furthermore, some tissues have more than one type of stem cell, each used in only particular situations of regenerative stress. Thus, there is no "one size fits all" adult tissue stem cell paradigm.

Figure 1. Lineage Tracing in Adult Tissue Stem Cell Systems

(A) A self-renewing stem cell is labeled with a specific marker (green). All cells in the hierarchy are permanently marked in long-term follow up. (B) Specific labeling of mature, differentiated cells. If these cells are replaced by a mature stem/progenitor, the label will disappear from the mature population with time. (C) A progenitor, not capable of indefinite self-renewal, is labeled. After short follow-up, multiple lineages are marked. However, the marked cells disappear after longer times.

Figure 2. Schematic of a System with Two Stem Cells

Both the active and reserve stem cells are capable of self-renewal. In most situations, including normal tissue maintenance, only the active stem cell contributes to renewal of the tissue, dividing continuously and giving rise to an amplifying compartment and mature cells. When the active stem cell is lost, a normally dormant (label-retaining) reserve stem cell is activated and replenishes the active stem cell compartment.