1. GFAP-directed Inactivation of Men1 Exploits Glial Cell Plasticity in Favor of Neuroendocrine Reprogramming
- Author
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Suzann Duan, Travis W. Sawyer, Ricky A. Sontz, Bradley A. Wieland, Andres F. Diaz, and Juanita L. Merchant
- Subjects
Hyperplasia ,Hepatology ,Carcinogenesis ,Cell Plasticity ,Gastroenterology ,Cell Differentiation ,Mice ,Neuroendocrine Cells ,Proto-Oncogene Proteins ,Gastrins ,Glial Fibrillary Acidic Protein ,Multiple Endocrine Neoplasia Type 1 ,Animals ,Hedgehog Proteins ,RNA, Small Interfering ,Neuroglia - Abstract
Efforts to characterize the signaling mechanisms that underlie gastroenteropancreatic neoplasms (GEP-NENs) are precluded by a lack of comprehensive models that recapitulate pathogenesis. Investigation into a potential cell-of-origin for gastrin-secreting NENs revealed a non-cell autonomous role for loss of menin in neuroendocrine cell specification, resulting in an induction of gastrin in enteric glia. Here, we investigated the hypothesis that cell autonomous Men1 inactivation in glial fibrillary acidic protein (GFAP)-expressing cells induced neuroendocrine differentiation and tumorigenesis.Transgenic GFAPGFAPGFAP-directed Men1 inactivation exploits glial cell plasticity in favor of neuroendocrine differentiation.
- Published
- 2022