Regaining self-renewal: actual and potential stem cells

Have you ever thought that transit-amplifying progenitor cells have the potential to repopulate the damaged stem cell niche through regaining self-renewal capability in vivo? According to András Simon and Jonas Frisén in Cell’s From Stem Cell to Progenitor and Back Again: “It has long been suspected that cells other than those that maintain homeostasis (actual stem cells) can take over stem cell function in certain situations, and they have been referred to as potential stem cells (Potten and Loeffler, 1990).” In a recent study in Developmental Cell, Nakagawa et al. (2007) pulse-labeled undifferentiated cells in the mouse male germline using an inducible genetic recombination system. Their results indicate that “the stem cells that maintain normal homeostasis do not appear to be the same cell population that repopulates the niche after transplantation and regeneration.” Indeed it seems that transit-amplifying progenitor cells are potential stem cells in this system and when actual stem cells are lost due to an injury or perhaps naturally over time, the remaining progenitor cells or progenitor cells acquired by transplantation have the potential to acquire stem cell functions.

Figure 7 from Nakagawa et al. (2007). A Model of the Spermatogenic Stem Cell Compartments

(A) In the normal round of spermatogenesis, the stem cell potential is not limited to the cells that actually self-renew in the stem cell niche (actual stem cells); also, part of the transit-amplifying cells that do not self-renew may possess the potential (potential stem cells). Both of these compartments are included in the undifferentiated spermatogonia entity.

(B) Upon loss of the actual stem cells, the potential stem cells would switch their mode from transit amplification to self-renewal, resulting in the genesis of the new actual stem cells (indicated by a red arrow). The emptied stem cell niche may play crucial roles in triggering this shift of mode. See text for details.