Pituitary stem cells: past, present and future perspectives

Pituitary cells that express the transcription factor SOX2 are stem cells because they can self-renew and differentiate into multiple pituitary hormone-producing cell types as organoids. Wounding and physiological challenges can activate pituitary stem cells, but cell numbers are not fully restored, and the ability to mobilize stem cells decreases with increasing age. The basis of these limitations is still unknown. The regulation of stem cell quiescence and activation involves many different signalling pathways, including those mediated by WNT, Hippo and several cytokines; more research is needed to understand the interactions between these pathways. Pituitary organoids can be formed from human or mouse embryonic stem cells, or from human induced pluripotent stem cells. Human pituitary organoid transplantation is sufficient to induce corticosterone release in hypophysectomized mice, raising the possibility of therapeutic applications. Today, pituitary organoids have the potential to assess the role of individual genes and genetic variants on hormone production ex vivo, providing an important tool for the advancement of exciting frontiers in pituitary stem cell biology and pituitary organogenesis. In this article, we provide an overview of notable discoveries in pituitary stem cell function and highlight important areas for future research. This Review discusses notable discoveries in pituitary stem cell function and highlights important areas for current and future research, including the use of pituitary organoids for the advancement of pituitary stem cell biology and pituitary organogenesis as well as potential therapeutic approaches. The cells of the anterior pituitary gland have a low turnover rate, and the tissue has a limited regenerative capacity.Pituitary stem cells secrete factors, such as WNT and Hippo, that initiate proliferation in adjacent cells; the recipient cells are probably guided to differentiate into specific hormone-producing cell types by hypothalamic input and/or end organ feedback.Organoids and 2D cultures derived from embryonic stem cells and induced pluripotent stem cell cultures show promise as tools for the study of differentiation ex vivo.Stem cells are known to exist in pituitary tumours, but the roles of these cells in tumour initiation, progression, recurrence and resistance to pharmacological therapy need to be further elucidated.