Next Article in Journal
Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention
Next Article in Special Issue
Analysis of Astroglial Secretomic Profile in the Mecp2-Deficient Male Mouse Model of Rett Syndrome
Previous Article in Journal
CHOP Pro-Apoptotic Transcriptional Program in Response to ER Stress Is Hacked by Zika Virus
Due to scheduled maintenance work on our core network, there may be short service disruptions on this website between 16:00 and 16:30 CEST on September 25th.
Review

Modeling Rett Syndrome with Human Pluripotent Stem Cells: Mechanistic Outcomes and Future Clinical Perspectives

1
Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
2
Associate Laboratory i4HB-Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
3
Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal
*
Author to whom correspondence should be addressed.
Academic Editor: Botond Penke
Int. J. Mol. Sci. 2021, 22(7), 3751; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073751
Received: 11 March 2021 / Revised: 23 March 2021 / Accepted: 2 April 2021 / Published: 3 April 2021
(This article belongs to the Special Issue Molecular Research on Rett Syndrome and Related Disorders)
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Among many different roles, MeCP2 has a high phenotypic impact during the different stages of brain development. Thus, it is essential to intensively investigate the function of MeCP2, and its regulated targets, to better understand the mechanisms of the disease and inspire the development of possible therapeutic strategies. Several animal models have greatly contributed to these studies, but more recently human pluripotent stem cells (hPSCs) have been providing a promising alternative for the study of RTT. The rapid evolution in the field of hPSC culture allowed first the development of 2D-based neuronal differentiation protocols, and more recently the generation of 3D human brain organoid models, a more complex approach that better recapitulates human neurodevelopment in vitro. Modeling RTT using these culture platforms, either with patient-specific human induced pluripotent stem cells (hiPSCs) or genetically-modified hPSCs, has certainly contributed to a better understanding of the onset of RTT and the disease phenotype, ultimately allowing the development of high throughput drugs screening tests for potential clinical translation. In this review, we first provide a brief summary of the main neurological features of RTT and the impact of MeCP2 mutations in the neuropathophysiology of this disease. Then, we provide a thorough revision of the more recent advances and future prospects of RTT modeling with human neural cells derived from hPSCs, obtained using both 2D and organoids culture systems, and its contribution for the current and future clinical trials for RTT. View Full-Text
Keywords: Rett syndrome; MeCP2; neurodevelopmental disorders; hPSCs; hiPSCs; 2D models; organoids Rett syndrome; MeCP2; neurodevelopmental disorders; hPSCs; hiPSCs; 2D models; organoids
Show Figures

Figure 1

MDPI and ACS Style

Gomes, A.R.; Fernandes, T.G.; Cabral, J.M.S.; Diogo, M.M. Modeling Rett Syndrome with Human Pluripotent Stem Cells: Mechanistic Outcomes and Future Clinical Perspectives. Int. J. Mol. Sci. 2021, 22, 3751. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073751

AMA Style

Gomes AR, Fernandes TG, Cabral JMS, Diogo MM. Modeling Rett Syndrome with Human Pluripotent Stem Cells: Mechanistic Outcomes and Future Clinical Perspectives. International Journal of Molecular Sciences. 2021; 22(7):3751. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073751

Chicago/Turabian Style

Gomes, Ana R., Tiago G. Fernandes, Joaquim M.S. Cabral, and Maria M. Diogo 2021. "Modeling Rett Syndrome with Human Pluripotent Stem Cells: Mechanistic Outcomes and Future Clinical Perspectives" International Journal of Molecular Sciences 22, no. 7: 3751. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073751

Find Other Styles
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