SOX9-positive pituitary stem cells differ according to their position in the gland and maintenance of their progeny depends on context

Stem cell (SC) differentiation and maintenance of resultant progeny underlie cell turnover in many organs, but it is difficult to pinpoint the contribution of either process. In the pituitary, a central regulator of endocrine axes, adult SCs undergo activation after target organ ablation, providing a well-characterized paradigm to study an adaptative response in a multi-organ system. Here, we used single-cell technologies to characterize SC heterogeneity and mobilization together with lineage tracing. We show that SC differentiation occurs more frequently than thought previously. In adaptative conditions, differentiation increases and is more diverse than demonstrated by the lineage tracing experiments. Detailed examination of SC progeny suggests that maintenance of selected nascent cells underlies SC output, highlighting a trophic role for the microenvironment. Analyses of cell trajectories further predict pathways and potential regulators. Our model provides a valuable system to study the influence of evolving states on the mechanisms of SC mobilization.