Stemness in the Niche

Reprogramming committed differentiated cells into stable stem cells has been achieved in various settings in vitro. A new study by Tata et al. (2013) demonstrates that, when airway basal stem cells are in demand, spontaneous reprogramming occurs in vivo as committed secretory cells convert into stem cells to replenish the stem cell pool. The authors use lineage-tracing strategies to show that, in response to the ablation of airway basal stem cells, secretory cells proliferate, acquire stem cell markers, and eventually generate a stable stem cell pool that gives rise to all three epithelial cell types of the airway. Although it is comforting to see that nature has a backup plan for compensating sudden stem cell loss, one can imagine that the hidden stemness potential of differentiated cells needs to be carefully controlled for the maintenance of tissue homeostasis. Indeed, Tata and colleagues find that direct contact with one single basal stem cell is sufficient to keep the dedifferentiation ability of secretory cells in a restful slumber. Moreover, their sphere-forming assays indicate that the stemness potential of different secretory cell subsets is inversely correlated with their relative maturity, in analogy to the reprogramming observed in the initial amphibian cloning experiments. Together, these findings demonstrate that this contingency plan for ensuring a functional basal stem cell pool is tightly regulated in both cell-autonomous and nonautonomous manners, which leads to the next question of how this mode of regulation is executed in the three-dimensional environment in vivo. Additionally, one wonders whether this remarkable spontaneous dedifferentiation ability might contribute to cancer. Tata, P.R., et al. (2013). Nature 503, 218–223.