Background: Using genetic lineage tracing in the mouse pituitary, we previously revealed that SOX2 positive cells can act as stem cells in vivo and contribute to all hormone-secreting cell types during postnatal life. However, SOX2-expressing stem cells are not the sole source of new endocrine cells, instead they complement contribution from more committed cell types during organ homeostasis.
Objective and hypotheses: We seek to determine key signalling mechanisms required to regulate organ turnover, since their disruption can underlie disease states e.g. organ failure or the formation of tumours. The WNT signalling pathway plays critical roles in stem cell function of many organs and pathway elevation in pituitary stem cells leads to tumours. Our aim is to understand the function of the WNT pathway during normal pituitary physiology, specifically if it is required for proliferation and to identify sources of WNT signals.
Method: By combining genetic and molecular approaches we are able to manipulate the WNT pathway in the pituitary and to label WNT-responsive cells and follow their fates.
Results: We find that WNT-responsive cells contribute the major source of new cells to organ turnover. Unexpectedly, we uncover that SOX2-expressing stem cells secrete WNT ligands, thus acting as critical regulators of homeostasis in a paracrine manner.
Conclusion: Pituitary stem cells contribute to the organ both directly through the generation of new cells, as well as indirectly through acting as essential niche cells promoting proliferation of more committed cell types. This represents a key step towards understanding the mechanisms controlling stimulation of new cell generation in situ, with an impact on future regenerative medicine approaches.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology