Lamin A/C Is Required for ChAT-Dependent Neuroblastoma Differentiation
| العنوان: | Lamin A/C Is Required for ChAT-Dependent Neuroblastoma Differentiation |
|---|---|
| المؤلفون: | Marta Nardella, Emanuele Cacci, Igea D'Agnano, Andrea Ennio Storti, Alessandra Valentini, Armando Felsani, Gabriella Augusti-Tocco, Mara D'Onofrio, Carla Musa, Stefano Biagioni, Loredana Guglielmi, Ilaria Iannetti, Ivan Arisi |
| المصدر: | Molecular neurobiology (Online) (2016). doi:10.1007/s12035-016-9902-6 info:cnr-pdr/source/autori:Guglielmi L1, Nardella M1, Musa C1, Iannetti I1, Arisi I2, D'Onofrio M2, Storti A2, Valentini A3, Cacci E4, Biagioni S4, Augusti-Tocco G4, D'Agnano I5, Felsani A6/titolo:Lamin A%2FC Is Required for ChAT-Dependent Neuroblastoma Differentiation/doi:10.1007%2Fs12035-016-9902-6/rivista:Molecular neurobiology (Online)/anno:2016/pagina_da:/pagina_a:/intervallo_pagine:/volume |
| بيانات النشر: | Spinger, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Transcription, Genetic, Cellular differentiation, Neuroscience (miscellaneous), LMNA, Tretinoin, Biology, Choline O-Acetyltransferase, Gene product, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, Neuroblastoma, Downregulation and upregulation, Choline acetyltransferase, Cell Line, Tumor, Protein Interaction Mapping, Gene expression, Animals, Receptors, Cholinergic, lamin A/C, Cell Proliferation, Neurons, Gene knockdown, Differentiation, Cell Cycle, Cell Differentiation, Lamin Type A, Receptors, Muscarinic, Molecular biology, Up-Regulation, Gene Expression Regulation, Neoplastic, Gene Ontology, 030104 developmental biology, Neurology, Gene Knockdown Techniques, Lamin |
| الوصف: | The mouse neuroblastoma N18TG2 clone is unable to differentiate and is defective for the enzymes of the biosynthesis of neurotransmitters. The forced expression of choline acetyltransferase (ChAT) in these cells results in the synthesis and release of acetylcholine (Ach) and hence in the expression of neurospecific features and markers. To understand how the expression of ChAT triggered neuronal differentiation, we studied the differences in genome-wide transcription profiles between the N18TG2 parental cells and its ChAT-expressing 2/4 derived clone. The engagement of the 2/4 cells in the neuronal developmental program was confirmed by the increase of the expression level of several differentiation-related genes and by the reduction of the amount of transcripts of cell cycle genes. At the same time, we observed a massive reorganization of cytoskeletal proteins in terms of gene expression, with the accumulation of the nucleoskeletal lamina component Lamin A/C in differentiating cells. The increase of the Lmna transcripts induced by ChAT expression in 2/4 cells was mimicked treating the parental N18TG2 cells with the acetylcholine receptor agonist carbachol, thus demonstrating the direct role played by this receptor in neuron nuclei maturation. Conversely, a treatment of 2/4 cells with the muscarinic receptor antagonist atropine resulted in the reduction of the amount of Lmna RNA. Finally, the hypothesis that Lmna gene product might play a crucial role in the ChAT-dependent molecular differentiation cascade was strongly supported by Lmna knockdown in 2/4 cells leading to the downregulation of genes involved in differentiation and cytoskeleton formation and to the upregulation of genes known to regulate self-renewal and stemness. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b41ddcd81470129e34eb332732a08550 http://hdl.handle.net/11573/950855 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b41ddcd81470129e34eb332732a08550 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |