Single-cell transcriptional profiling of young adult and old mouse anterior pituitary after transgenically inflicted local damage

Adult pituitary stem cells (SC) are mainly dormant, yet in the case of damage the resident SC compartment shows swift activation. More in particular, following diphtheria toxin (DT)-triggered endocrine cell-ablation injury in the GHCre/iDTR mouse model (expressing the Cre recombinase under control of the Gh promoter, as well as the Cre-inducible DT receptor (iDTR)), the pituitary stem cell population is promptly activated displaying enhanced proliferative activity and expansion. Substantial regeneration of the depleted somatotropes is eventually observed after 5 to 6 months. However, this regenerative competence rapidly drops with age, and is no longer observed when mice get older (from 8-10 months of age). Virtually nothing is known about the molecular machinery driving the quiescent pituitary stem cells into activation (as observed following local injury), neither about how this route may change at advancing age. Here, we started to tackle this query by interrogating young (9-11 weeks) and old (14 months), damaged and undamaged pituitary (specifically, its major endocrine AP lobe) using single-cell RNA sequencing. We focused on the prompt stem cell reaction that occurs immediately upon the DT-induced local damage in the GHCre/iDTR model.