Functions of Stem Cells in Pituitary Plasticity

University Of California, San Diego, La Jolla CA

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Abstract

DESCRIPTION (provided by applicant): The pituitary gland is an endocrine organ that secretes hormones to control various vital processes throughout the body, including growth during childhood, the stress response, sexuality, reproduction, metabolic homeostasis, and lactation. It dynamically changes its relative cell number and hormone secretion activity to meet the endocrine needs in response to a variety of physiological and pathological challenges. The molecular mechanism that regulates pituitary plasticity is not well understood. Recently pituitary stem cells have been identified and in vivo lineage tracing experiments revealed that these stem cells contribute almost exclusively to postnatal pituitary growth and homeostatic maintenance under basal condition. However, their roles in pituitary plasticity are completely unknown, and whether or not these cells are functionally required under pathological conditions await to be determined. In addition, there is evidence suggesting that postnatal pituitary stem cells are distinct from pituitary embryonic progenitor cells. Therefore, the central focus of this application is to characterize postnatal pituitary stem cells with respect to their pattern of gene expression and their functionality. The postnatal pituitary stem cells, as well as embryonic pituitary progenitor cells, will be isolated and their gene expression profiling will be performed using massively parallel sequencing technology and further compared to have a comprehensive understanding of unique features of these stem cells. The investigators will be poised to further explore the regulatory networks that control pituitary stem cells self-renewal and differentiation. In addition, they have recently generated a mouse model that lacks entire postnatal pituitary stem cell population. This mouse model will be employed to assess the in vivo function of stem cells in pituitary plasticity. PUBLIC HEALTH RELEVANCE: Malfunction of the pituitary gland, including underproduction (hypopituitarism) or overproduction (pituitary tumors) of hormones lead to more than a dozen disorders of the endocrine system and has serious consequences for human health and quality of life. Pituitary stem cells have been implicated in pituitary postnatal growth, homeostatic maintenance, pituitary plasticity, and pituitary tumors. Molecular and functional characterization of pituitary stem cells will greatly enhance our understanding of dynamic regulation of pituitary functions and potentially provide novel mechanisms of pituitary dysfunction and pituitary tumors.