Pituitary stem cells differ according to their position in the gland and maintenance of their progeny depends on physiological context

Stem cell (SC) differentiation and maintenance of resultant progeny underlie regeneration in many organs, but it is difficult to pinpoint contribution of either process. In the pituitary, a central regulator of endocrine axes, a population of adult SCs undergo activation following target organ ablation, providing a well-characterized paradigm to study regeneration in a multiorgan system. Here we used single cell technologies to characterize SC heterogeneity and regeneration modalities. We consequently performed lineage tracing experiments. Our result show that SC differentiation occurs more frequently than previously thought. In regenerative conditions, differentiation is both increased and more diverse than lineage tracing experiments demonstrated. Detailed examination of SC progeny demonstrate that nascent cells maintenance is an important regulatory step controlling SC-derived regeneration, highlighting a trophic role for the microenvironment. Analyses of cell trajectories further predict modalities, and potential new players involved in regeneration. Our model provides a unique system to study the influence of evolving physiological states on the mechanisms of SC regeneration. Teaser Pituitary stem cells are heterogeneous and differentiate more than formerly thought but maintenance of their progeny is selective.