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

Abstract: Stem cell (SC) differentiation and maintenance of the resultant nascent cells underlie regeneration in many organs, but it is often difficult to pinpoint contribution of either process to SC output. In the pituitary gland, a central regulator of endocrine axes, a population of adult SCs undergo activation following target organ ablation in the mouse, providing a well-characterized paradigm to study regeneration in a multi-organ system. Here we have used single cell technologies to characterize both heterogeneity of this population and modalities of regeneration. We consequently performed short and long-term lineage tracing experiments based on our transcriptomic analyses predictions. 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 had formerly demonstrated. Examination of SC progeny at different time points demonstrate that, while differentiation is indeed relatively frequent, maintenance of the nascent cells is an important regulatory step controlling SC-derived regeneration, reconciliating our data with previous observations and highlighting a trophic role for the microenvironment. Analyses of cell trajectories and gene regulatory networks (GRNs) further predict modalities, and identifies potential new players involved in regeneration. Our model provides a unique system to study the influence of evolving physiological states on the mechanisms of regeneration from SCs.