Endocrine Abstracts

Tissue-specific progenitors play essential roles for organ development and homeostasis but they are not present in all tissues. Throughout life, the pituitary gland adapts the proportion of its endocrine cell types to meet hormonal demands. This plasticity may rely on adult progenitor cells and we have recently described such a population. These cells express SOX2, an HMG box transcription factor, marker of several embryonic progenitors and stem cells, and form ‘pituispheres’ in culture, which can grow, self renew, and differentiate to all pituitary endocrine cells. Differentiation is associated with expression of SOX9, a related HMG box factor. SOX2^+ve cells are found throughout Rathke’s pouch in embryos and persist in the adult gland. However most of these adult SOX2^+ve cells also express SOX9. This SOX2^+ve/SOX9^+ve population may represent transit amplifying cells, whereas the SOX2^+ve/SOX9^−ve cells could be progenitor/stem cells. In order to prove this hypothesis and also better characterize the newly developed pituisphere cultures we are currently following different approaches. We have first undertaken lineage marker analysis in order to prove that SOX2^+ve cells give rise to endocrine cells in vivo. We are also developing genetic tools to specifically inactivate Sox2 and Sox9 to understand their function in the embryonic and adult pituitary and to learn more about the cells in which they are expressed. Finally, to establish the pituisphere culture as an in vitro system to understand endocrine cell differentiation we are currently developing assays to manipulate/control differentiation of specific endocrine lineages.