Next Article in Journal
The Effects of Proteasome Inhibitors on Telomerase Activity and Regulation in Multiple Myeloma Cells
Next Article in Special Issue
Adult Stem Cell Functioning in the Tumor Micro-Environment
Previous Article in Journal
Epigenetic Mechanisms in Hepatic Stellate Cell Activation During Liver Fibrosis and Carcinogenesis
Previous Article in Special Issue
Thrombin Preconditioning Enhances Therapeutic Efficacy of Human Wharton’s Jelly–Derived Mesenchymal Stem Cells in Severe Neonatal Hypoxic Ischemic Encephalopathy
Open AccessArticle

Senescence Phenomena and Metabolic Alteration in Mesenchymal Stromal Cells from a Mouse Model of Rett Syndrome

1
Department of Advanced Medical and Surgical Sciences, Center for Rare Diseases and Inter University Center for Research in Neurosciences, University of Campania “Luigi Vanvitelli”, via Sergio Pansini, 5, 80131 Naples, Italy
2
Department of Experimental Medicine, Campania University “Luigi Vanvitelli”, via Santa Maria di Costantinopoli, 16, 80138 Naples, Italy
3
Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, BioLife Building (015-00)1900 North 12th Street, Temple University, Philadelphia, PA 19122-6078, USA
4
Research Institute on Terrestrial Ecosystems, National Research Council, via Pietro Castellino, 111, 80131 Naples, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(10), 2508; https://doi.org/10.3390/ijms20102508
Received: 31 March 2019 / Revised: 17 May 2019 / Accepted: 19 May 2019 / Published: 21 May 2019
(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration)
Chromatin modifiers play a crucial role in maintaining cell identity through modulation of gene expression patterns. Their deregulation can have profound effects on cell fate and functions. Among epigenetic regulators, the MECP2 protein is particularly attractive. Mutations in the Mecp2 gene are responsible for more than 90% of cases of Rett syndrome (RTT), a progressive neurodevelopmental disorder. As a chromatin modulator, MECP2 can have a key role in the government of stem cell biology. Previously, we showed that deregulated MECP2 expression triggers senescence in mesenchymal stromal cells (MSCs) from (RTT) patients. Over the last few decades, it has emerged that senescent cells show alterations in the metabolic state. Metabolic changes related to stem cell senescence are particularly detrimental, since they contribute to the exhaustion of stem cell compartments, which in turn determine the falling in tissue renewal and functionality. Herein, we dissect the role of impaired MECP2 function in triggering senescence along with other senescence-related aspects, such as metabolism, in MSCs from a mouse model of RTT. We found that MECP2 deficiencies lead to senescence and impaired mitochondrial energy production. Our results support the idea that an alteration in mitochondria metabolic functions could play an important role in the pathogenesis of RTT. View Full-Text
Keywords: Rett syndrome; mesenchymal stromal cells; senescence; DNA repair; metabolism; ATP levels; mitochondrial ATP; autophagy; proteasome Rett syndrome; mesenchymal stromal cells; senescence; DNA repair; metabolism; ATP levels; mitochondrial ATP; autophagy; proteasome
Show Figures

Graphical abstract

MDPI and ACS Style

Squillaro, T.; Alessio, N.; Capasso, S.; Di Bernardo, G.; Melone, M.A.B.; Peluso, G.; Galderisi, U. Senescence Phenomena and Metabolic Alteration in Mesenchymal Stromal Cells from a Mouse Model of Rett Syndrome. Int. J. Mol. Sci. 2019, 20, 2508.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop