Endocrine Abstracts

The pituitary gland harbors stem cells whose role and regulation remain poorly understood. We recently established organoids from (mouse) pituitary as a novel research model to study pituitary stem cell biology (Cox et al., J Endocrinol 2019). Organoids represent 3D in vitro cell structures that self-develop from tissue stem cells under defined culture conditions, and that reproduce multiple aspects of the original healthy or diseased tissue. Organoids are long-term expandable while retaining their characteristics. The pituitary organoids originate from the SOX2⁺stem cells, retain this stemness phenotype during expansive culture and show specific (still limited) hormonal differentiation capacity. This novel organoid model is now used to decipher pituitary stem cell biology at key time points of life as well as after pituitary perturbation (such as transgenic damage which provokes a regenerative response). The endometrium undergoes hormone-regulated cycles of growth, differentiation, degeneration and regeneration. Little is known on the mechanisms that govern these biological remodeling processes, which go awry in endometrial pathology. We established organoid models from healthy human (and mouse) endometrium which were found to display physiological hormone responsiveness, thereby reproducing the menstrual cycle in a dish (Boretto et al., Development 2017). In addition, we derived organoids from a broad spectrum of endometrial pathologies ranging from hyperplasia to high-grade cancer (Boretto et al., Nature Cell Biology 2019). The organoids capture the heterogeneity of the disease, both in vitro and in vivo, and recapitulate genomic abnormalities of the patient’s primary tumor. They exhibit disease-specific gene expression signatures and show patient-dependent drug responses. Hence, the new organoid biobank can serve as drug-screening platform to identify better and novel therapies, even in a patient-tailored manner (personalized medicine). In conclusion, we created novel organoid research models for pituitary and endometrium which will be highly valuable to gain more insight into the tissue’s biology and pathology.