Definitive evidence for the presence or absence of an adrenomedullary stem cell has been enigmatic to date, but we have recently identified the presence of a bona fide stem cell population in this organ. Renewal of the catecholamine-secreting chromaffin cell population of the adrenal medulla is necessary for physiological homeostasis throughout life, but the signals controlling the cell fate decisions of adrenomedullary stem cells as well as their descendant chromaffin cells are not known. Using genetic approaches in mouse, human adrenomedullary stem cell culture and single cell approaches, this project aims to discern the signalling mechanisms that govern cell fate decisions in this organ, with an emphasis on stem cell regulation. Our recent research on the pituitary gland has revealed that stem cells of this endocrine organ act as signalling hubs, controlling the cell fate decisions of their neighbouring cells through paracrine secretion. The project will explore if this type of regulation also applies to adrenomedullary stem cells. Finally, the project will determine if the critical mechanisms identified are perturbed in the tumours pheochromocytoma and paraganglioma, and if they may underlie the aetiology and pathogenesis of the initial steps of tumour formation. This knowledge will have the potential to open up new treatment avenues.
(i) Dissect the signalling mechanisms that control homeostasis in the adrenal medulla.
(ii) Determine if the non-classical, paracrine contribution of stem cells is important for the regulation of cell fate decisions in the adrenal medulla.
(iii) Identify new signalling mechanisms involved adrenomedullary tumour formation and perturb these in vitro and in vivo.
Molecular biology, mouse genetics and husbandry, histology, immunofluorescence, mRNA in situ hybridisation, dissections primary tissue culture, computational analysis using R.