Stem cells are undifferentiated cells capable of self-renewal and differentiating into all the other cell types within a tissue. For decades biologists have believed that stem cells are key for understanding regeneration and repair. However, the number of differentiated cells is vast compared to the tiny speck that a stem cells is. Moreover, many stem cells spend most of their time in a dormant state without producing progeny. How can a small group of highly dormant cells generate the large bulk of tissues needed for daily wear and tear, or replace damaged tissues? It turns out that stem cells generate transit-amplifying cells (TACs), a highly proliferative progeny, to expand the system and produce diverse cell types downstream.

For a long time the function of TACs was largely neglected. TACs were viewed as a passive population that just cranks out tissues. In a recent review in WIREs Developmental Biology, Ya-Chieh Hsu, assistant professor of Stem Cell and Regenerative Biology at Harvard University, and Bing Zhang, a postdoctoral fellow in the Hsu Lab and first author on the paper, summarized recent progresses that challenge this view. By cross-comparing regenerating hair follicles and the blood system, the authors elaborated the importance of TACs. First, TACs are directly responsible for generating a large amount of diverse progeny within a tissue. Second, TACs perform critical regulatory roles in tissue regeneration by influencing stem cell activity and niche remodeling. Third, TACs also play an important role in oncogenesis.

Zhang and Hsu conclude, “We are expecting to see more examples showing the critical functions of TACs in other tissues, since TACs are the true workforce for tissue production, not stem cells. If we want to development treatment for a variety of diseases through manipulating tissue production, we need to understand a lot more about the cells that actually do the job.”

Contributed by Ya-Chieh Hsu and Bing Zhang