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Updated: Jul 5, 2025

Development of Organoids from Mouse Pituitary as In Vitro Model to Explore Pituitary Stem Cell Biology
Published on: February 25, 2022
Glycoprotein hormone subunit alpha 2 (GPHA2): A pituitary stem cell-expressed gene associated with NOTCH2 signaling
Xiyu Ge1, Karen Weis1, Lori Raetzman2
1Department of Molecular and Integrative Physiology, University of Illinois Urbana-Champaign, 524 Burrill Hall, 407 South Goodwin Avenue, Urbana, IL, 61801, USA.
Abstract:
NOTCH2 is expressed in pituitary stem cells and is necessary for stem cell maintenance, proliferation, and differentiation. However, the pathways NOTCH2 engages to affect pituitary development remain unclear. In this study, we hypothesized that glycoprotein hormone subunit A2 (GPHA2), a corneal stem cell factor and ligand for the thyroid stimulating hormone receptor (TSHR), is downstream of NOTCH2 signaling. We found Gpha2 is expressed in quiescent pituitary stem cells by RNAscope in situ hybridization and scRNA seq. In Notch2 conditional knockout pituitaries, Gpha2 mRNA is reduced compared with control littermates. We then investigated the possible functions of GPHA2. Pituitaries treated with a GPHA2 peptide do not have a change in proliferation. However, in dissociated adult pituitary cells, GPHA2 increased pCREB expression and this induction was reversed by co-treatment with a TSHR inhibitor. These data suggest GPHA2 is a NOTCH2 related stem cell factor that activates TSHR signaling, potentially impacting pituitary development.
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