Notch-Dependent Pituitary SOX2+ Stem Cells Exhibit a Timed Functional Extinction in Regulation of the Postnatal Gland

• Notch signaling is necessary to maintain Sox2+ stem cells in the pituitary gland
• Sox2+ cells and differentiated cells contribute to postnatal pituitary expansion
• Sox2+ stem cells prove to be dispensable for adult pituitary gland homeostasis
• Differentiated cells retain mitotic capacity and respond to physiological demands

SummaryAlthough SOX2+ stem cells are present in the postnatal pituitary gland, how they are regulated molecularly and whether they are required for pituitary functions remain unresolved questions. Using a conditional knockout animal model, here we demonstrate that ablation of the canonical Notch signaling in the embryonic pituitary gland leads to progressive depletion of the SOX2+ stem cells and hypoplastic gland. Furthermore, we show that the SOX2+ stem cells initially play a significant role in contributing to postnatal pituitary gland expansion by self-renewal and differentiating into distinct lineages in the immediate postnatal period. However, we found that within several weeks postpartum, the SOX2+ stem cells switch to an essentially dormant state and are no longer required for homeostasis/tissue adaptation. Our results present a dynamic tissue homeostatic model in which stem cells provide an initial contribution to the growth of the neonatal pituitary gland, whereas the mature gland can be maintained in a stem cell-independent fashion.

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