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dc.creatorSquillaro, T
dc.creatorAlessio, N
dc.creatorCipollaro, M
dc.creatorMelone, MAB
dc.creatorHayek, G
dc.creatorRenieri, A
dc.creatorGiordano, A
dc.creatorGalderisi, U
dc.date.accessioned2021-01-31T22:24:30Z
dc.date.available2021-01-31T22:24:30Z
dc.date.issued2012-04-15
dc.identifier.issn1059-1524
dc.identifier.issn1939-4586
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/5448
dc.identifier.other22357617 (pubmed)
dc.identifier.urihttp://hdl.handle.net/20.500.12613/5466
dc.description.abstractMECP2 protein binds preferentially to methylated CpGs and regulates gene expression by causing changes in chromatin structure. The mechanism by which impaired MECP2 activity can induce pathological abnormalities in the nervous system of patients with Rett syndrome (RTT) is not clearly understood. To gain further insight into the role of MECP2 in human neurogenesis, we compared the neural differentiation process in mesenchymal stem cells (MSCs) obtained from a RTT patient and from healthy donors. We further analyzed neural differentiation in a human neuroblastoma cell line carrying a partially silenced MECP2 gene. Senescence and reduced expression of neural markers were observed in proliferating and differentiating MSCs from the RTT patient, which suggests that impaired activity of MECP2 protein may impair neural differentiation, as observed in RTT patients. Next, we used an inducible expression system to silence MECP2 in neuroblastoma cells before and after the induction of neural differentiation via retinoic acid treatment. This approach was used to test whether MECP2 inactivation affected the cell fate of neural progenitors and/or neuronal differentiation and maintenance. Overall, our data suggest that neural cell fate and neuronal maintenance may be perturbed by senescence triggered by impaired MECP2 activity either before or after neural differentiation. © 2012 Squillaro et al.
dc.format.extent1435-1445
dc.language.isoen
dc.relation.haspartMolecular Biology of the Cell
dc.relation.isreferencedbyAmerican Society for Cell Biology (ASCB)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0
dc.subjectCell Line, Tumor
dc.subjectCellular Senescence
dc.subjectChromatin
dc.subjectCpG Islands
dc.subjectDNA Methylation
dc.subjectGene Expression Regulation
dc.subjectHumans
dc.subjectMesenchymal Stem Cells
dc.subjectMethyl-CpG-Binding Protein 2
dc.subjectNeuroblastoma
dc.subjectNeurogenesis
dc.subjectNeurons
dc.subjectRNA Interference
dc.subjectRNA, Small Interfering
dc.subjectRett Syndrome
dc.subjectTretinoin
dc.titleReduced expression of MECP2 affects cell commitment and maintenance in neurons by triggering senescence: New perspective for Rett syndrome
dc.typeArticle
dc.type.genreJournal Article
dc.relation.doi10.1091/mbc.E11-09-0784
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.creator.orcidGiordano, Antonio|0000-0002-5959-016X
dc.date.updated2021-01-31T22:24:26Z
refterms.dateFOA2021-01-31T22:24:31Z


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