TY - JOUR
T1 - Glycoprotein hormone subunit alpha 2 (GPHA2)
T2 - A pituitary stem cell-expressed gene associated with NOTCH2 signaling
AU - Ge, Xiyu
AU - Weis, Karen E
AU - Raetzman, Lori
N1 - The authors wish to thank Leah Nantie for initial experimental assistance and Dr. Erik Nelson for providing guidance and reagents as we began dissociated cell culture and GPHA2 peptide treatment. This work was supported by the National Institutes of Health [ R01 DK076647 ] and the University of Illinois Research Board [ RB22092 ].
PY - 2024/5/15
Y1 - 2024/5/15
N2 - 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.
AB - 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.
KW - Gpha2
KW - Notch signaling
KW - Pituitary development
KW - Stem cell
KW - TSH receptor
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U2 - 10.1016/j.mce.2024.112163
DO - 10.1016/j.mce.2024.112163
M3 - Article
C2 - 38246572
AN - SCOPUS:85186314430
SN - 0303-7207
VL - 586
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
M1 - 112163
ER -