دورية أكاديمية
GFAP-directed Inactivation of Men1 Exploits Glial Cell Plasticity in Favor of Neuroendocrine Reprogramming
| العنوان: | GFAP-directed Inactivation of Men1 Exploits Glial Cell Plasticity in Favor of Neuroendocrine Reprogramming |
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| المؤلفون: | Duan, S., Sawyer, T.W., Sontz, R.A., Wieland, B.A., Diaz, A.F., Merchant, J.L. |
| المساهمون: | University of Arizona College of Medicine, Department of Medicine, Division of Gastroenterology, Wyant College of Optical Sciences, University of Arizona |
| المصدر: | Cellular and Molecular Gastroenterology and Hepatology |
| بيانات النشر: | Elsevier Inc. |
| سنة النشر: | 2022 |
| المجموعة: | The University of Arizona: UA Campus Repository |
| مصطلحات موضوعية: | Enteric Glia, Gastrinomas, Hedgehog Signaling, KIF3A, Primary Cilia, SOX10 |
| الوصف: | Background & Aims: 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. Methods: Transgenic GFAPΔMen1 mice were generated by conditional GFAP-directed Men1 deletion in GFAP-expressing cells. Cre specificity was confirmed using a tdTomato reporter. GFAPΔMen1 mice were evaluated for GEP-NEN development and neuroendocrine cell hyperplasia. Small interfering RNA-mediated Men1 silencing in a rat enteric glial cell line was performed in parallel. Results: GFAPΔMen1 mice developed pancreatic NENs, in addition to pituitary prolactinomas that phenocopied the human MEN1 syndrome. GFAPΔMen1 mice exhibited gastric neuroendocrine hyperplasia that coincided with a significant loss of GFAP expression. Men1 deletion induced loss of glial-restricted progenitor lineage markers and an increase in neuroendocrine genes, suggesting a reprogramming of GFAP+ cells. Deleting Kif3a, a mediator of Hedgehog signaling, in GFAP-expressing cells attenuated neuroendocrine hyperplasia by restricting the neuroendocrine cell fate. Similar results in the pancreas were observed when Sox10 was used to delete Men1. Conclusions: GFAP-directed Men1 inactivation exploits glial cell plasticity in favor of neuroendocrine differentiation. © 2022 The Authors ; Open access journal ; This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2352-345X |
| العلاقة: | Duan, S., Sawyer, T. W., Sontz, R. A., Wieland, B. A., Diaz, A. F., & Merchant, J. L. (2022). GFAP-directed Inactivation of Men1 Exploits Glial Cell Plasticity in Favor of Neuroendocrine Reprogramming. Cellular and Molecular Gastroenterology and Hepatology, 14(5), 1025–1051.; http://hdl.handle.net/10150/666872Test; Cellular and Molecular Gastroenterology and Hepatology |
| DOI: | 10.1016/j.jcmgh.2022.06.009 |
| الإتاحة: | https://doi.org/10.1016/j.jcmgh.2022.06.009Test http://hdl.handle.net/10150/666872Test |
| حقوق: | Copyright © 2022 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0Test/). ; https://creativecommons.org/licenses/by-nc-nd/4.0Test |
| رقم الانضمام: | edsbas.366D0D31 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2352345X |
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| DOI: | 10.1016/j.jcmgh.2022.06.009 |