Investigating the role of NFI transcription factors in Pituitary Stem Cells (360G-Wellcome-228316_Z_23_Z)

The pituitary gland controls important functions such a growth, metabolism, our response to stress as well as puberty and reproduction. Since it is important to maintain steady hormone levels, the pituitary replenishes hormone-producing endocrine cells throughout life. These cells are derived from stem cells that express a factor called SOX2. Our research has shown that the function of these stem cells declines with age in mice, which may contribute to the loss of pituitary function. Additionally, it has shown that abnormal function of stem cells can result in tumours of the pituitary. YAP/TAZ signalling is critical in pituitary stem cells (PSCs), as it underlies a switch between homeostatic function and the generation of tumours, but the mechanisms that control the PSC state are not known. Computational analyses of a YAP overexpression model, predicted that the Nuclear Factor I (NFI) family of transcription factors (TFs), previously undescribed in the pituitary, are key candidate factors in controlling the stem cell state. I will explore the function on NFI factors in the regulation of PSCs. This is based on the hypothesis that NFIs together with SOX2 and YAP are part of a regulatory network that promote the stem cell fate in the pituitary.